Idiopathic membranous nephropathy: an autoimmune disease.

For more than 50 years researchers have debated the evidence for an autoimmune basis of human idiopathic membranous nephritis (MN). Work published in the past 2 years has substantially strengthened the belief that MN is indeed an autoimmune disease of the kidney. Autoantibodies of the IgG4 subclass to at least three podocyte membrane proteins including phospholipase A(2)-receptor, aldose reductase, and manganese superoxide dismutase have been detected by immunoblotting in sera as well as in acid eluates prepared from renal biopsy tissue of patients with this disease, using either whole tissue or microdissected glomeruli from frozen sections.

Intravenous clusterin administration reduces myocardial infarct size in rats.

Background: Clusterin (Apolipoprotein J), a plasma protein with cytoprotective and complement-inhibiting activities, localizes in the infarcted heart during myocardial infarction (MI). Recently, we have shown a protective effect of exogenous clusterin in vitro on ischaemically challenged cardiomyocytes independent of complement. We therefore hypothesized that intravenous clusterin administration would reduce myocardial infarction damage.

Routes to covalent catalysis by reactive selection for nascent protein nucleophiles.

Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests the universal utility of the covalent complex as the basis for selection.

Intramolecular epitope spreading in Heymann nephritis.

Immunization with megalin induces active Heymann nephritis, which reproduces features of human idiopathic membranous glomerulonephritis. Megalin is a complex immunological target with four discrete ligand-binding domains (LBDs) that may contain epitopes to which pathogenic autoantibodies are directed. Recently, a 236-residue N-terminal fragment, termed "L6," that spans the first LBD was shown to induce autoantibodies and severe disease.

Albumin-stimulated TGFbeta-1 in renal tubular cells is associated with activation of MAP kinase.

Background: Proteinuric renal diseases are often associated with progressive tubulointerstitial fibrosis that usually defines the degree and rate of progression of renal failure. Glomerular filtration of excess albumin, the dominant protein in proteinuria, into proximal tubule could provide the stimulus to induce certain fibrogenic cytokines from proximal tubular cells (PTC), which may account for fibrosis in the interstitium. To explore this hypothesis we tested the effect of bovine albumin in PTC in culture on the expression and secretion of transforming growth factor (TGF) beta-1, a prominent fibrogenic cytokine.

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes syndrome with hypothyroidism and focal segmental glomerulosclerosis in a paediatric patient.

Herein, we report on a paediatric patient with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who was hospitalized for acute on chronic renal insufficiency, seizures and deterioration of the level of consciousness. She also had hypertension, hypothyroidism and nephrotic range proteinuria. Kidney biopsy revealed many sclerotic glomeruli and focal segmental glomerulosclerosis (FSGS).

Nested N-terminal megalin fragments induce high-titer autoantibody and attenuated Heymann nephritis.

It was shown previously that an N-terminal fragment (nM60) that encompasses amino acid residues 1 to 563 of megalin could induce active Heymann nephritis (AHN) as efficiently as the native protein. For delineation of a minimal structure within this fragment that is sufficient to induce AHN, smaller protein fragments that encompass residues 1 to 236 (L6), 1 to 195 (L5), 1 to 156 (L4), and 1 to 120 (L3), representing successive C-terminal truncations within ligand-binding repeats of nM60, were cloned and produced in a baculovirus insect cell expression system. Protein fragments L4, L5, and L6 clearly were glycosylated.

Bilateral infundibulopelvic stenosis without renal insufficiency: is surgery necessary?

The following case describes the clinical course of a patient with bilateral infundibulopelvic stenosis from her initial presentation at age 2 through the age of 14 years. This condition is associated with hypoplasia of segments of the upper collecting system and is characterized by dilated calyces that drain through stenotic infundibulae. Our patient is unique in that, although her renal function has slowly deteriorated with time, she has a persistently non-obstructive pattern on dynamic imaging studies.

Conformation and glycosylation of a megalin fragment correlate with nephritogenicity in Heymann nephritis.

Active Heymann nephritis (AHN), a rat model of autoimmune glomerulonephritis, is induced by immunization with autologous megalin, a 600-kDa cell surface glycoprotein isolated from crude renal extracts. Recombinant proteins containing a 563-residue N-terminal sequence of megalin were obtained from Escherichia coli and baculovirus-insect cell expression systems. Rats immunized with the soluble, secreted protein encoded by a baculovirus construct elicited high titer anti-megalin autoantibodies and developed glomerular immune deposits and elevated proteinuria consistent with AHN.

Treatment of membranous nephropathy in children.

Membranous nephropathy (MN) is not a common pediatric glomerular disease and not a common cause of idiopathic nephrotic syndrome (NS) in children. Because of the rarity of the disease, there is only a limited amount of uncontrolled data and no controlled data available in children regarding the treatment of MN. Older uncontrolled data indicate that nearly a quarter of children with NS, whether untreated or treated with various immunosuppressive agents, develop chronic renal failure.

Pilot study describing the use of pravastatin in pediatric renal transplant recipients.

Renal transplant (Tx) recipients frequently develop hypercholesterolemia. Pravastatin (P) has been shown to be effective in adult renal Tx recipients, not only in reducing serum cholesterol, but possibly also in decreasing graft rejection. However, there are no data on the use of P in children following renal transplantation.

Life-threatening extrarenal lupus in children despite improvement in serologic findings.

Systemic lupus erythematosus (SLE) is an autoimmune disorder with the potential for multiorgan involvement. Serologic tests are helpful in establishing the diagnosis of SLE and predicting disease flares. However, there are few data on the relationship between the onset of new organ involvement and lupus serologies, especially in children.

Microhematuria after renal transplantation in children.

The renal transplant (Tx) recipient is at risk for developing various complications including urolithiasis, the only manifestation of which may be hematuria. However, there are no data on the prevalence of microscopic hematuria in renal Tx recipients. The objective of our study was to determine the prevalence of microhematuria in our pediatric Tx patients and to investigate the causes of microhematuria.

Early and late recipient graft function and donor outcome after laparoscopic vs open adult live donor nephrectomy for pediatric renal transplantation.

Background: Laparoscopically procured live donor kidney grafts are increasingly transplanted into pediatric recipients. The safety and efficacy of this changed surgical practice are unknown.

Hypothesis: Outcomes of laparoscopic vs open donor grafts in recipients 18 years and younger are equivalent.

QTc interval in children with chronic renal failure and with renal transplants.

Prolongation of the QTc interval, a risk factor for cardiac arrhythmias, has been observed in adult hemodialysis patients; there are few data on the QTc interval in children with chronic renal failure (CRF) and following renal transplantation (Tx). The purpose of our study was to determine the QTc interval in children with CRF and post renal Tx. Twenty children with CRF and 16 children with renal Tx who were followed at the University of California, Davis, underwent prospective EKG monitoring.

A small N-terminal 60-kD fragment of gp600 (megalin), the major autoantigen of active Heymann nephritis, can induce a full-blown disease.

Active Heymann nephritis of rat, an autoimmune glomerular disease, is an immunohistological, ultrastructural, and clinical model of human membranous glomerulonephritis. Both diseases in their full-blown form are characterized by (1) the formation of large, subepithelial glomerular immune deposits, which stain for IgG, C3, and membrane attack (C5b-9) components of complement and (2) the excretion of large amounts of protein in the urine (proteinuria). The target autoantigen of active Heymann nephritis is a large transmembrane renal glycoprotein with a molecular weight of approximately 600 kD, variously named gp600, gp330, LRP-2, or "megalin.