Galactose-Deficient IgA1 B cells in the Circulation of IgA Nephropathy Patients Carry Preferentially Lambda Light Chains and Mucosal Homing Receptors.

Background: IgA nephropathy (IgAN) primary glomerulonephritis is characterized by the deposition of circulating immune complexes composed of polymeric IgA1 molecules with altered O-glycans (Gd-IgA1) and anti-glycan antibodies in the kidney mesangium. The mesangial IgA deposits and serum IgA1 contain predominantly light (L) chains, but the nature and origin of such IgA remains enigmatic.

Methods: We analyzed L chain expression in peripheral blood B cells of 30 IgAN patients, 30 healthy controls (HCs), and 18 membranous nephropathy patients selected as disease controls (non-IgAN).

Multiparametric flow cytometry analysis of peripheral blood B cell trafficking differences among Epstein-Barr virus infected and uninfected subpopulations.

Aims: Epstein-Barr virus (EBV) targets predominantly B cells and these cells could acquire new phenotype characteristics. Here we analyzed whether EBV-infected and -uninfected B cells from healthy subjects differ in proportion of dominant phenotypes, maturation stage, and homing receptors expression.

Methods: EBV-infected and -uninfected cells were identified by flow cytometry using fluorophore-labeled EBV RNA-specific DNA probes combined with fluorophore-labeled antibody to surface lineage markers, integrins, chemokine receptors, and immunoglobulin isotypes, including intracellular ones.

Glucocorticoids Reduce Aberrant O-Glycosylation of IgA1 in IgA Nephropathy Patients.

Background/aims: IgA nephropathy is associated with aberrant O-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibitors or angiotensin II blockers, corticosteroids are recommended.

[IgA nephropathy - research-generated questions].

IgA nephropathy (IgAN) is the most common type of glomerulonephritis. Its etiology involves an increased production of polymeric immunoglobulin A1 with an abnormal composition of some carbohydrate chains. The reaction of these abnormal forms of IgA1 with specific autoantibodies while circulating immune complexes arise and settle in the renal mesangium with subsequent inflammatory activation of mesangial cells which in up to 50% of cases results in end-stage kidney failure.

[Metabolic acidosis in chronic kidney disease].

Metabolic acidosis (MAC) is a constant symptom of chronic kidney disease (CKD) in advanced stages. However, its onset and degree do not depend only on the decrease of glomerular filtration but also on tubular functions. Therefore, in patients with predominant tubulointerstitial involvement it may already appear in earlier stages of CKD, usually as MAC with normal anion gap.

[[Na+] - [Cl-] difference significantly contributes to acidemia in patients with liver cirrhosis].

Aim: To evaluate the role of strong ion difference (SID) in acid-base disorders in patients with liver disease.

Patients And Methods: We evaluated the acid-base status in 11 patients with liver cirrhosis both by traditional and quantitative Stewart-Fencl methods.

Results: Nine of eleven patients had pH within the norm, 2/11 had pH above 7.

[Clinical evaluation of acid-base status: Henderson-Hasselbalch, or Stewart-Fencl approach?].

Two approaches have been used in clinical evaluation the acid-base status: traditional (bicarbonate-centered) is based on the Henderson-Hasselbalch equation complemented by calculation of the anion gap, and more recent quantitative approach proposed by Stewart and Fencl. The latter method defines the three independent variables, which regulate pH. These include: the difference between the sum of charges carried by strong plasma cations and anions termed the strong ion difference - SID (decrease causes acidosis, and vice versa); the total concentration of the weak non-volatile acids [Atot] (inorganic phosphate and albumin, decrease causes alkalosis and vice versa), and pCO2.

Acid-base disorders associated with serum electrolyte patterns in patients on hemodiafiltration.

Background: Metabolic acidosis (MAC) is a common aspect of dialysis-dependent patients. It is definitely caused by acid retention; however, the influence of other plasma ions is unclear. Understanding the mechanism of MAC and its correction is important when choosing the dialysis solution.

[IgA Nephropathy. Facts, uncertainties, and potential causal therapy approaches].

IgA nephropathy is currently the most frequently investigated glomerulonephritis. The disease is defined by the presence of dominant or co-dominant deposits of IgA1 in the glomerular mesangium. Circulating immune complexes are most likely the source of the deposited IgA1.

IgA nephropathy: molecular mechanisms of the disease.

Studies of molecular and cellular interactions involved in the pathogenesis of IgA nephropathy have revealed the autoimmune nature of this most common primary glomerulonephritis. In patients with this disease, altered glycan structures in the unique hinge region of the heavy chains of IgA1 molecules lead to the exposure of antigenic determinants, which are recognized by naturally occurring antiglycan antibodies of the IgG and/or IgA1 isotype. As a result, nephritogenic immune complexes form in the circulation and deposit in the glomerular mesangium.

Malignant Wegener's granulomatosis with fibrosing mediastinitis and vena cava superior syndrome.

A 47-year-old man was admitted to hospital for migratory joint pain, fatigue, and cough with bloody sputum and proteinuria with increased serum creatinine level. Diagnosis of Wegener's granulomatosis was established. During follow-up, the vena cava superior syndrome developed.

IgA1 immune complexes from pediatric patients with IgA nephropathy activate cultured human mesangial cells.

Background: Circulating immune complexes (CIC) containing galactose (Gal)-deficient IgA1 from adults with IgA nephropathy (IgAN) induce proliferation of cultured mesangial cells, but activities of CIC from pediatric patients with the disease have not been studied.

Methods: CIC of different sizes were isolated from sera of pediatric and adult IgAN patients and their effects on cultured human mesangial cells (MC) were assessed by measuring cellular proliferation, expression of IL-6 and IL-8 and laminin and phosphotyrosine signaling.

Results: Large CIC from pediatric IgAN patients (>800 kDa) containing Gal-deficient IgA1 stimulated cellular proliferation, whereas in some patients, smaller CIC were inhibitory.

Contribution of Jan Brod to nephrology.

Jan Brod (1912-1985), Professor of Medicine of Charles University, Prague, was one of the outstanding personalities of the Czechoslovak medicine and European nephrology of the 20th century. He was an eminent clinician, teacher and scientist who belonged among the founders of renal medicine in Europe. He grew up in the scientific tradition of Prague and Vienna and he was trained by some outstanding personalities, particularly Paul Wood.

Effect of donor/recipient body weight ratio, donor weight, recipient weight and donor age on kidney graft function in children.

Background: We hypothesized that supplementing a higher mass of renal parenchyma from adult donors, and their younger age, would improve graft function in paediatric recipients.

Methods: We calculated estimated glomerular filtration rate (eGFR; Schwartz formula) and absolute glomerular filtration rate (absGFR) in 57 renal-grafted children (1995-2007) aged 3.1-17.

Urinary transforming growth factor-β1 in children with obstructive uropathy.

Aim: Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor-β1 (TGF-β1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF-β1 levels in children with obstructive and non-obstructive uropathies (NOU).

Acid-base balance in peritoneal dialysis patients: a Stewart-Fencl analysis.

Background: Evaluation of acid-base disorders using the Stewart-Fencl principle is based on assessment of independent factors: strong ion difference (SID) and the total concentration of non-volatile weak acids (Atot). This approach allows for a more detailed evaluation of the cause of acid-base imbalance than the conventional bicarbonate-centered approach based on the Henderson-Hasselbalch principle, which is a necessary yet insufficient condition to describe the state of the system. The aim of our study was to assess acid-base disorders in peritoneal dialysis (PD) patients using both of these principles.

Urinary tract infections in pediatric renal transplant recipients--a two center risk factors study.

UTI are common in renal Tx recipients and may significantly impact on the graft function. The aim of our study was to evaluate the prevalence, risk factors, and significance of UTI in Tx children. We performed a retrospective cross-sectional study of 76 Tx patients, median age at Tx was 13.

IgA nephropathy: current views of immune complex formation.

Characteristic features of IgA nephropathy (IgAN) include IgA1-containing immune complexes (IC) in the circulation, urine, and renal mesangium. IC contain IgA1 deficient in hinge region-associated galactose (Gal) and antibodies specific for antigenic determinants present on the hinge region. The biological effects of IC are primarily related to their molecular size and composition: when added to a culture of human mesangial cells, large IC exhibit a proliferative effect while small complexes are inhibitory.

IgA nephropathy: a clinical overview.

Our understanding of the clinical aspects of IgA nephropathy (IgAN) has advanced since the 10th International Symposium on IgA Nephropathy in 2004. In this review we discuss new developments in areas of familial IgAN, the emerging field of biomarkers, and prognostic features. Familial disease continues to account for a significant number of newly diagnosed patients with IgAN.