C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of membranoproliferative glomerulonephritis classified as C3 glomerulopathies. These conditions are characterized by an increased number of intraglomerular cells and diffuse thickening of the glomerular capillary walls, along with the deposition of C3 and minimal or absent immunoglobulin deposits. The underlying cause of both DDD and C3Gn is an abnormal activation of the alternative complement pathway, which can result from acquired or genetic alteration. In acquired forms of DDD and C3GN, the dysregulation of the alternative pathway is commonly induced by the presence of C3 nephritic factors (C3NeFs), which are autoantibodies that stabilize C3 convertase. Both DDD and C3GN can affect individuals of any age, but DDD is primarily diagnosed in children, whereas C3GN tends to be diagnosed at a significantly higher age. The presenting features of these diseases are variable and may include proteinuria, hematuria, hypertension, or kidney failure. A common finding in these diseases is low serum C3 levels with normal serum C4 levels. Chronic deterioration of renal function is commonly observed in DDD and C3GN, often leading to end-stage renal disease (ESRD), especially in DDD. Kidney transplantation outcomes in patients with these conditions are characterized by histological recurrence, which may contribute to higher rates of allograft failure

Renal involvement in eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis, which typically affects small-to medium-sized blood vessels. It is characterized by the presence of tissue infiltrates rich in eosinophils, along with the formation of granulomatous lesions. About 40% of cases have positive anti-neutrophil cytoplasm antibodies (ANCA), with predominant perinuclear staining, and anti-myeloperoxidase (anti-MPO) specificity in about 65% of cases. Typical manifestations of EGPA include the late onset of asthma, nasal and sinus-related symptoms, peripheral neuropathy, and significant eosinophilia observed in the peripheral blood. In contrast to granulomatosis with polyangiitis and microscopic polyangiitis, renal involvement in EGPA is less frequent (about 25%) and poorly studied. Necrotizing pauci-immune crescentic glomerulonephritis is the most common renal presentation in patients with ANCA-positive EGPA. Although rarely, other forms of renal involvement may also be observed, such as eosinophilic interstitial nephritis, mesangial glomerulonephritis, membranous nephropathy, or focal sclerosis. A standardized treatment for EGPA with renal involvement has not been defined, however the survival and the renal outcomes are usually better than in the other ANCA-associated vasculitides. Nonetheless, kidney disease is an adverse prognostic factor for EGPA patients. Larger studies are required to better describe the renal involvement, in particular for patterns different from crescentic glomerulonephritis, and to favor the development of a consensual therapeutic approach. In this article, in addition to personal data, we will review recent findings on patient clinical phenotypes based on ANCA, genetics and the impact of biological drugs on disease management

Modulation of Myostatin/Hepatocyte Growth Factor Balance by Different Hemodialysis Modalities

Background. In this study we investigated the relevance of myostatin and Hepatocyte Growth Factor (HGF) in patients undergoing hemodialysis HD and the influence of different HD modalities on their levels. Methods. We performed a prospective crossover study in which HD patients were randomized to undergo 3-month treatment periods with bicarbonate hemodialysis (BHD) followed by online hemodiafiltration (HDF). Clinical data, laboratory parameters, and myostatin and HGF serum levels were collected and compared. Results. Ten patients and six controls (C) were evaluated. In any experimental condition myostatin and HGF levels were higher in HD than in C. At enrollment and after BHD there were not significant correlations, whereas at the end of the HDF treatment period myostatin and HGF were inversely correlated (r -0.65, p<0.05), myostatin serum levels inversely correlated with transferrin (r -0.73, p<0.05), and HGF levels that resulted positively correlated with BMI (r 0.67, p<0.05). Moving from BHD to HDF, clinical and laboratory parameters were unchanged, as well as serum HGF, whereas myostatin levels significantly decreased (6.3 \ub1 4.1 versus 4.3 \ub1 3.1 ng/ml, p<0.05). Conclusions. Modulation of myostatin levels and myostatin/HGF balance by the use of different HD modalities might represent a novel approach to the prevention and treatment of HD-related muscle wasting syndrome

ANCA-associated vasculitis in childhood: Recent advances

Abstract Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are rare systemic diseases that usually occur in adulthood. They comprise granulomatosis with polyangiitis (GPA, Wegener’s), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Their clinical presentation is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in childhood but North-American and European cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. Herein, we review the main clinical and therapeutic aspects of childhood-onset ANCA-associated vasculitis, and provide preliminary data on demographic characteristics and organ manifestations of an Italian multicentre cohort

Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome.

BACKGROUND: Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome. METHODS: We screened patients with microscopic  polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction 25% as compared with diagnosis, while 4/34 (12%) had started RRT. CONCLUSIONS: AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression

A continuous, non-convex & sparse super-resolution approach for fluorescence microscopy data with Poisson noise

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A continuous, non-convex & sparse super-resolution approach for fluorescence microscopy data with Poisson noise

We propose a non-convex sparsity-promoting variational model for the problem of super-resolution in Single Molecule Localization Microscopy (SMLM). Namely, we study a continuous non-convex relaxation of a non-continuous and non-convex variational model where a weighted-L2 data fidelity modeling signal-dependent Poisson noise is combined with an L0-regularization to promote signal sparsity. The proposed relaxation is obtained by adapting the Continuous Exact L0 (CEL0) relaxation of the analogous `2`0 problem with Gaussian noise to the Poisson scenario, which is more realistic in fluorescence microscopy applications. The associated optimization problem is then solved by an iterative reweighted L1 (IRL1) algorithm. The weighted-L2 data fidelity leads to a challenging estimation of the algorithmic parameters for which efficient computation strategies are detailed. To validate our approach, we report qualitative and quantitative localization results for a simulated dataset, showing that the proposed weighted-CEL0 (WCEL0) model is well suited and capable to deal with Poisson measurements with high accuracy and precision

Modular-proximal gradient algorithms in variable exponent Lebesgue spaces

International audienceWe consider structured optimisation problems defined in terms of the sum of a smooth and convex function, and a proper, l.s.c., convex (typically non-smooth) one in reflexive variable exponent Lebesgue spaces $L^{p(.)}(\Omega)$. Due to their intrinsic space-variant properties, such spaces can be naturally used as solution space and combined with space-variant functionals for the solution of ill-posed inverse problems. For this purpose, we propose and analyse two instances (primal and dual) of proximal gradient algorithms in $L^{p(.)}(\Omega)$., where the proximal step, rather than depending on the natural (non-separable) $L^{p(.)}(\Omega)$. norm, is defined in terms of its modular function, which, thanks to its separability, allows for the efficient computation of algorithmic iterates. Convergence in function values is proved for both algorithms, with convergence rates depending on problem/space smoothness. To show the effectiveness of the proposed modelling, some numerical tests highlighting the flexibility of the space $L^{p(.)}(\Omega)$. are shown for exemplar deconvolution and mixed noise removal problems. Finally, a numerical verification on the convergence speed and computational costs of both algorithms in comparison with analogous ones defined in standard $L^{p(.)}(\Omega)$. spaces is presented

Weighted-CEL0 sparse regularisation for molecule localisation in super-resolution microscopy with Poisson data

International audienceWe propose a continuous non-convex variational model for Single Molecule Localisation Microscopy (SMLM) super-resolution in order to overcome light diffraction barriers. Namely, we consider a variation of the Continuous Exact $\ell_0$ (CEL0) penalty recently introduced to relax the $\ell_2-\ell_0$ problem where a weighted-$\ell_2$ data fidelity is considered to model signal-dependent Poisson noise. For the numerical solution of the associated minimisation problem, we consider an iterative reweighted $\ell_1$ (IRL1) strategy for which we detail efficient parameter computation strategies. We report qualitative and quantitative molecule localisation results showing that the proposed weighted-CEL0 (wCEL0) model improves the results obtained by CEL0 and state-of-the art deep-learning approaches for the high-density SMLM ISBI 2013 dataset

Modular-proximal gradient algorithms in variable exponent Lebesgue spaces

We consider structured optimisation problems defined in terms of the sum of a smooth and convex function, and a proper, l.s.c., convex (typically non-smooth) one in reflexive variable exponent Lebesgue spaces $L^{p(.)}(\Omega)$. Due to their intrinsic space-variant properties, such spaces can be naturally used as solution space and combined with space-variant functionals for the solution of ill-posed inverse problems. For this purpose, we propose and analyse two instances (primal and dual) of proximal gradient algorithms in $L^{p(.)}(\Omega)$., where the proximal step, rather than depending on the natural (non-separable) $L^{p(.)}(\Omega)$. norm, is defined in terms of its modular function, which, thanks to its separability, allows for the efficient computation of algorithmic iterates. Convergence in function values is proved for both algorithms, with convergence rates depending on problem/space smoothness. To show the effectiveness of the proposed modelling, some numerical tests highlighting the flexibility of the space $L^{p(.)}(\Omega)$. are shown for exemplar deconvolution and mixed noise removal problems. Finally, a numerical verification on the convergence speed and computational costs of both algorithms in comparison with analogous ones defined in standard $L^{p(.)}(\Omega)$. spaces is presented