Explore the vast range of titles available.

BackgroundIn Henoch–Schönlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable.MethodsWe evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up.ResultsBetween the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p < 0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053).ConclusionsOur results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.

Background Histological findings from primary kidney biopsies were correlated with patient outcomes in a national cohort of paediatric Henoch–Schönlein nephritis (HSN) patients. Methods Primary kidney biopsies from 53 HSN patients were re-evaluated using the ISKDC (International Study of Kidney Disease in Children) classification and a modified semiquantitative classification (SQC) that scores renal findings and also takes into account activity, chronicity and tubulointerstitial indices. The ISKDC and SQC classifications were evaluated comparatively in four outcome groups: no signs of renal disease (outcome A, n  = 27), minor urinary abnormalities (outcome B, n  = 18), active renal disease (outcome C, n  = 3) and renal insufficiency, end-stage renal disease or succumbed due to HSN (outcome D, n  = 5). For the receiver operating characteristic and logistic regression analyses, outcomes A and B were considered to be favourable and outcomes C and D to be unfavourable. The median follow-up time was 7.3 years. Results The patients with an unfavourable outcome (C and D), considered together due to low patient numbers, had significantly higher total biopsy SQC scores and activity indices than those who had a favourable one (groups A and B). The chronicity and tubulointerstitial indices differed significantly only between group C + D and group A. The difference in areas under the curve between the total biopsy SQC scores and ISKDC findings was 0.15 [ p  = 0.04, normal-based 95% confidence interval (CI) 0.007–0.29, bias-controlled 95% CI −0.004 to 0.28]. Conclusions Our results suggest that the modified SQC is more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Type XIII collagen is a type II transmembrane protein found at sites of cell adhesion. Transgenic mouse lines were generated by microinjection of a DNA construct directing the synthesis of truncated α1(XIII) chains. Shortened α1(XIII) chains were synthesized by fibroblasts from mutant mice, and the lack of intracellular accumulation in immunofluorescent staining of tissues suggested that the mutant molecules were expressed on the cell surface. Transgene expression led to fetal lethality in offspring from heterozygous mating with two distinct phenotypes. The early phenotype fetuses were aborted by day 10.5 of development due to a lack of fusion of the chorionic and allantoic membranes. The late phenotype fetuses were aborted by day 13.5 of development and displayed a weak heartbeat, defects of the adherence junctions in the heart with detachment of myofilaments and abnormal staining for the adherence junction component cadherin. Decreased microvessel formation was observed in certain regions of the fetus and the placenta. These results indicate that type XIII collagen has an important role in certain adhesive interactions that are necessary for normal development.

We evaluated the natural long-term outcome after childhood IgA nephritis. Altogether 55 patients with biopsy-proven IgA nephritis were identified, 37 (67%) responded to the health questionnaire and 31 (56%) participated in the medical examination after a mean follow-up of 18.7 years (SD 6.2; range 8.5-29.8). The results of medical examination, onset data and the re-analysis of original biopsies of 31 participants were used when analyzing the predictive factors for persistent nephropathy, i.e. constant proteinuria/hematuria or end-stage renal disease (ESRD). All patients' medical history data were obtained from regional hospitals and renal survival data from the national kidney register. Six (11%) of the 55 identified patients had developed ESRD. Sixteen (52%) of the 31 participants were not attending for regular follow-up visits after the acute phase. Twenty-two (71%) had renal symptoms and 12 (39%) were receiving drugs for hypertension/proteinuria at their latest follow-up visit. The chronicity index and total biopsy score in the first renal biopsy were higher in patients with persistent nephropathy or ESRD than in those without (p=0.022 and p=0.014, respectively). Nine (69%) of the 13 subjects who had been over 16 years of age at diagnosis had persistent nephropathy or ESRD, compared with 4 (22%) of the 18 subjects who had been under 16 years of age (relative risk 3.1, 95% CI 1.2-8.0). Pregnancy complications were common: 12 (55%) of the 22 pregnancies had been complicated by proteinuria and/or hypertension, and the prematurity rate was 30%. Long-term follow-up during adulthood is needed even after mild childhood IgA nephritis, especially in women during and after pregnancy.

Insufficient reepithelialization of injured alveolar walls may be important in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Laminin-5 is expressed in epithelial cells of healing wounds, promoting cell attachment and migration. In this study we have studied the extent of reepithelialization of newly formed intraluminal connective tissue, the immunohistochemical expression and ultrastructural localization of the laminin-5 γ2 chain protein, and the synthesis of the laminin-5 γ2 chain mRNA in regenerating epithelial cells in cryptogenic organizing pneumonia (COP) and IPF. The results show that the mean extent of reepithelialization of intraluminal connective tissue lesions was 76% (SD, ± 27%) in COP, and 54% (SD, ± 23%) in IPF (p < 0.025). The laminin-5 γ2 chain was synthesized and widely expressed in regenerating epithelial cells in both diseases. Immunohistochemistry for surfactant-associated protein A suggests a pneumocyte origin for the regenerating epithelial cells in IPF. It is concluded that both in COP and IPF, regenerating epithelial cells are capable of synthesizing the laminin-5 γ2 chain needed for adhesive connections to the underlying basement membrane. However, in IPF, the reepithelialization seems to be disturbed or delayed.

Knowledge about how to treat severe Henoch–Schönlein nephritis (HSN) is scarce. The aim of our study is to compare cyclosporine A (CyA) and methylprednisolone pulses (MP) in the treatment of severe HSN. Out of 24 pediatric HSN patients with nephrotic-range proteinuria or crescentic HSN in kidney biopsy, seven were randomized to receive CyA for 12 months at an initial dose of 5 mg/kg and eight to receive 3 MP pulses of 30 mg/kg followed by prednisone for 4 months. The other nine patients received identical treatment without randomization. Kidney biopsies were performed at inclusion and after 2 years. The primary outcomes were the duration of proteinuria and hematuria, estimated glomerular filtration rate, and renal biopsy histology. All the 11 CyA-treated patients achieved resolution of nephrotic-range proteinuria within 3 months, while the MP-group response was slower, and in 6/13 was not achieved with the initial treatment. Additional immunosuppressive treatment was needed in none of the CyA-treated patients but in six patients treated with MP (difference in proportion 46%, p  = 0.008). The 2-year control biopsies were similarly improved in both groups. After mean 6.1 years (2.2–10.4 years), 16 patients (eight CyA, eight MP) had no renal symptoms and six (three CyA, three MP) had persistent nephropathy but normal renal function. One MP-treated patient had reduced renal function and another had developed ESRD and received a renal transplant. CyA gave a 100% resolution of nephrotic-range proteinuria and a 100% renal survival rate without additional therapy after a mean follow-up of 6 years. Treatment of HSN with CyA is efficacious, safe and not inferior to MP.

The kidney filtration barrier consists of the capillary endothelium, the glomerular basement membrane and the slit diaphragm localized between foot processes of neighbouring podocytes. We report that collagen XVII, a transmembrane molecule known to be required for epithelial adhesion, is expressed in podocytes of normal human and mouse kidneys and in endothelial cells of the glomerular filtration barrier. Immunoelectron microscopy has revealed that collagen XVII is localized in foot processes of podocytes and in the glomerular basement membrane. Its role in kidney has been analysed in knockout mice, which survive to birth but have high neonatal mortality and skin blistering and structural abnormalities in their glomeruli. Morphometric analysis has shown increases in glomerular volume fraction and surface densities of knockout kidneys, indicating an increased glomerular amount in the cortex. Collagen XVII deficiency causes effacement of podocyte foot processes; however, major slit diaphragm disruptions have not been detected. The glomerular basement membrane is split in areas in which glomerular and endothelial basement membranes meet. Differences in the expression of collagen IV, integrins α3 or β1, laminin α5 and nephrin have not been observed in mutant mice compared with controls. We propose that collagen XVII has a function in the attachment of podocyte foot processes to the glomerular basement membrane. It probably contributes to podocyte maturation and might have a role in glomerular filtration.

Two N-terminal ends of human type XVIII collagen chains have recently been identified. The two chains have different signal peptides and variant N-terminal noncollagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share 301 residues of their NC1 domains as well as the collagenous and C-terminal noncollagenous portions of the molecule. Antibodies were produced against the NC1 region common to both human α1(XVIII) chain variants and against NC1 sequences specific to the long variant and were used in combination with in situ hybridization to localize this collagen in a number of human tissues. They were also used for Western blotting, which resulted in detection of overlapping high-molecular weight bands above the 200-kd standard in a kidney extract. Heparin lyase II and heparin lyase III digestions of kidney and placenta extracts indicated that at least in these tissues, type XVIII collagen contains heparin sulfate glycosaminoglycan side chains. Type XVIII collagen was found to be a ubiquitous basement membrane component, occurring prominently at vascular and epithelial basement membranes throughout the body. Comparison of the expression of the NC1-493 and NC1-303 variants revealed marked differences. The short variant was found in most conventional basement membranes, including blood vessels and the various epithelial structures, and around muscular structures. The long variant was expressed very strongly in liver, where it was virtually the only variant in the liver sinusoids, and it occurred only in minor amounts elsewhere. Thus, the 192 N-terminal residues specific to the long variant apparently confer some functional property needed above all in the liver sinusoids, but also at certain other locations.

We evaluated the efficacy of cyclosporin A (CyA) for treating pediatric patients with severe Henoch-Schönlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria. Seven pediatric HSP-GN patients (5 boys, 2 girls) were treated with CyA, with a mean age of 10.6 years at diagnosis (range 7.2-15.2 years) and mean follow-up times of 6.0 years (range 4.4-8.9 years) from diagnosis and 5.2 years (range 3.4-7.7 years) from the beginning of the CyA treatment. All had developed nephrotic-range proteinuria within 1-3 months of the HSP diagnosis. A renal biopsy was performed on all the patients, and two showed rapidly progressive glomerulonephritis. They all received additional angiotensin converting enzyme inhibitor medication and one to three types of immunosuppressive treatment had been tried in five of the seven patients before CyA was initiated at a mean interval of 0.7 years after diagnosis (range 0.1-2.0 years). All the patients responded to the CyA treatment within a mean of 1.4 months (range 1 week to 4 months). Four patients achieved a stable remission and had been without CyA treatment for a mean of 3.7 years (range 2.9-5.3 years) by the end of the follow-up. Three patients seemed to become CyA dependent, since they developed proteinuria when the treatment was stopped. CyA treatment had been started significantly earlier ( P=0.045) in the former group (mean 0.2 years, range 0.1-0.3 years) than in the latter (mean 1.5 years, range 1.2-2.0 years). Renal function was preserved in all patients, the glomerular filtration rate, plasma cystatin C, serum albumin, and serum creatinine being within normal limits at the end of the follow-up. We conclude that CyA treatment for severe treatment-resistant HSP-GN is promising, since four of the seven patients enjoy stable remission and all have retained their renal function after a mean follow-up of 6.0 years. However, some patients seem to develop CyA-dependent nephritis.