Form Of Chronic Glomerulonephritis Research Articles

Comparison of administration of single- and triple-course steroid pulse therapy combined with tonsillectomy for immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis that can cause end-stage renal disease. Recently, tonsillectomy combined with corticosteroid pulse (TSP) has been shown to be effective for achieving clinical remission and favorable renal outcome in patients with IgAN. However, the standard regimen of corticosteroid use in TSP has not been established. Herein, we compared the effect of single- or triple-course steroid pulse therapy combined with tonsillectomy in patients with IgAN.This retrospective, observational cohort study included 122 patients with IgAN enrolled from January 2004 to December 2018 at 2 independent institutions. We divided the patients into 2 groups; single-course (TSP1: n = 70) and triple-course (TSP3: n = 52) of corticosteroid pulse therapy (1 course comprised 3 consecutive days’ infusion of 0.5 g methylprednisolone) combined with tonsillectomy. The primary outcome for renal survival was defined as the first occurrence of ≧30% decrease in estimated glomerular filtration rate from baseline. Secondary outcomes included the incidence of clinical remission and recurrence of the disease.Regarding clinical parameters and findings at baseline, there were no significant differences between the 2 groups. The 8-years renal survival in the 2 groups was not significantly different according to Kaplan–Meier curves (TSP1; 82.5% vs TSP3; 69.2%, log-rank test P = .39). The cumulative incidence rates of remission of hematuria (94.4% vs 85.4%, P = .56) and clinical remission (85.0% vs 64.8%, P = .07) were comparable in both groups, while those of proteinuria showed higher rates in TSP1 than TSP3 (88.4% vs 65.4%, P = .02). The cumulative incidence of relapse of hematuria (5.6% vs 2.3%, P = .42) and proteinuria (7.1% vs 3.3%, P = .41) showed no significant differences in the 2 groups. Cox regression analyses showed that the number of courses of corticosteroid pulse therapy was not significantly associated with renal outcome (TSP1 vs TSP3; Hazard ratios 0.69, 95% confidence intervals 0.29-1.64, P = .39).The effect of single-course corticosteroid pulse therapy is not statistically, significantly different from triple-course in TSP protocol for improving renal outcome and preventing relapse in patients with IgAN. Single-course corticosteroid pulse therapy may become a treatment option for patients with IgAN.

P0313POLYCLONAL FREE LIGHT CHAINS IN IGA-NEPHROPATHY: CORRELATION WITH CLINICAL AND MORPHOLOGICAL PARAMETERS AND PROGNOSTIC SIGNIFICANCE.

Abstract Background and Aims Mechanisms of kidney injury by monoclonal free light chains in myeloma kidney are well established. The role polyclonal free light chains (pFLC) in pathogenesis of renal interstitial inflammation and fibrosis in primary glomerulonephritis is still poorly investigated. We hypothesize that increased level of pFLC could have the similar role in activation of interstitial inflammation and fibrosis formation and impact chronic kidney disease (CKD) progression in the most prevalent form of chronic glomerulonephritis - IgA-nephropathy (IgAN). The aim of this retrospective study was to analyze the association of pFLC kappa (pFLC-κ) and lambda (pFLC-λ) assessed in serum by Freelite® with clinical and morphological parameters and CKD progression in IgA-nephropathy cohort. Method In this study we enrolled 23 patients with biopsy-confirmed diagnosis of IgAN. pFLC-κ and pFLC-λ levels were assessed in all cases at the time of kidney biopsy (KBx) by Freelite method. Normal range for pFLC-κ and pFLC-λ was 3,3-19,4 mg/l and 5,7-26,3 mg/l, respectively. The following clinical parameters were evaluated at the time of KBx: estimated glomerular filtration rate (eGFR) by CKD-EPI, daily proteinuria, serum albumin and microhematuria. Morphological findings were investigated by light and immunofluorescence (IgA, IgM, IgG, C3, C1, lambda, kappa, fibrinogen) microscopy. Oxford MEST-C score was evaluated as well as % of sclerotic glomeruli. Additionally we semiquantitatively measured (0- absent, 1- mild, 2 – moderate, 3 - severe) mesangial proliferation, endocapillary proliferation, glomerular basement membrane (GBM) thickening, interstitial inflammation, interstitial edema, tubular atrophy (TA), peritubular capillaritis (PTC), interstitial fibrosis (IF) according to currently accepted criteria. The demographic, clinical and morphological parameters at the time of KBx are presented in Table 1. Patients were treated with nephroprotective agents (n=23) and steroids/cyclophosphamide (n=21). Correlation between parameters were assessed by Spearman’s coefficient. Progression of CKD was determined as decline of eGFR >25% from the initial level at the end of follow-up period. Prognostic analysis was performed with Cox proportional hazards regression. Median follow-up was 28 (7; 37) months. Results Correlations between clinical and morphological parameters and pFLC levels are presented in Table 2. Univariate Cox regression analysis has shown that pFLC-κ (Exp(β)=1,051; 95% CI: 1,001-1,104, p=0,045) and FLC- λ (Exp(β)=1,040; 95% CI: 1,001-1,081, p=0,044) as well as other well-known clinical (daily proteinuria (Exp(β)=1,177; 95% CI: 1,003-1,382, p=0,045), eGFR at the KBx time (Exp(β)=2,981; 95% CI:1,112-20,124, p=0,042)) and morphological parameters (% of sclerotic glomeruli (Exp(β)=1,031; 95% CI: 1,001-1,062, p=0,046), T-score (Expβ=10,784; 95% СI: 1,364-85,246, p=0,024) are associated with CKD progression. Conclusion In IgAN higher levels of pFLC, both kappa and lambda, are associated with renal interstitial inflammation and fibrosis, tubular atrophy and chronic glomerular injury and could be used as predictors of CKD progression. Mechanisms of pFLC effects on the formation of renal tubular and interstitial inflammation and fibrosis require further studies.

Hyperlipidemia in chronic glomerulonephritis

The article presents materials on the effect of dyslipidemia in various clinical forms of chronic glomerulonephritis. In order to study this work, 88 patients with a confirmed diagnosis of chronic GN were examined. The effect of duration, gender, disease activity on the clinical forms of chronic GN, the state of the lipid spectrum on various clinical forms of chronic glomerulonephritis is analyzed. Analysis of the blood lipid spectrum of patients with chronic GN showed that the blood lipid spectrum in the first 5 years of the disease was different from the control, but with the progression of the disease by more than 5 years, there was a significant increase in all atherogenic lipid spectrum parameters. Spectrum, and with an increase in the duration of the disease, an increase in these indicators is observed, HDL, on the contrary, tended to decrease.

EVALUATION OF THE INTERRELATIONS OF BLOOD VCAM-1 LEVEL AND CLINICO-MORPHOLOGICAL CHARACTERISTICS OF CHRONIC GLOMERULONEFRITIS

Chronic glomerulonephritis is characterized by irreversible progression of the pathological process, which leads to the formation of terminal renal failure significantly impairing the patient's quality of life, leading to internal dysfunction and increasing the risk of premature overall and cardiovascular mortality. Consequently, the search for non-invasive methods for assessing the state of renal tissue, including the detection of proteins involved in renal inflammation, fibrosis, intercellular interaction is currently important.THE AIM: To determine the serum levels of the vascular cell adhesion molecule-1 (VCAM-1) in patients with various forms of chronic glomerulonephritis (CGN) and to clarify its relationship to the development of morphological changes in the renal tissue.PATIENTS AND METHODS: In 80 patients (men and women), with CGN in the acute stage was carried out a detailed clinical and laboratory examination, including determination of serum VCAM-1 by ELISA and performing puncture renal biopsy with the assessment of morphological changes. Statistical analysis of the results was carried out using «Microsoft Office Excel 2010» («Microsoft Corp.», USA) and "STATISTICA 10.0" («StatSoft Inc.», USA).RESULTS. The serum level concentration of VCAM-1 was 719 [643;771] ng/ml. Obtained statistically significant interrelations with enlargement of mesangial space, endothelial growth, capillary walls thickening, mesangial hypercellularity, endothelial hypercellularity, protein casts in tubules, anses capillaries union, fibrose demilunes, podocyte necrosis, hypertrophic remodeling type of resistive type vessels, Ig deposites, IgA deposites, IgG seposites, C3 complement fluorescence, fibrinogen deposites. CONCLUSION: The results of the study demonstrate the important role of VCAM-1 in the development of immunocomplex inflammation in glomerulonephritis. VCAM-1 is a marker of different morphological changes in CGN, and determining the level of VCAM-1 in serum is informative, simple and noninvasive method which provides evaluation of inflammatory process activity, prediction of the risk of morphological changes in the renal tissue structure in patients with CGN.

Состояние системы глутатиона у детей с нефротической формой хронического гломерулонефрита

Состояние системы глутатиона у детей с нефротической формой хронического гломерулонефрита

Role of mass-spectrometry in diagnostics of chronic glomerulonephritis

Objective: Early diagnostics and prognosis of the risk of renal pathology allow modulating of approaches of prophylaxis and treatment that, in turn, affects both life expectancy and standards of living. The goal of this study was to reveal the markers of pathological process in patients with renal pathology using noninvasive techniques. Methods: The study involved 13 patients: 6 males and 7 females (average age 37 years) with different morphological variants of chronic glomerulonephritis. The remote molecular diagnostic pattern was obtained for each biological sample using Ultraflex II TOF/TOF device (Bruker, United States) on the basis of MALDI-TOF-МС. Also, the «Expect» analysis was carried out for each protein. Identification of peptides and proteins in urine was performed in on-line regime followed by analysis of their primary structure and 3D structure. Results: It was found out that four patients with IgA-nephropathy possessed receptors VI of renal blood vessels to Tolloid-like-2 protein (TILL2) that is considered to be a risk factor of arterial hypertension. TILL2 protein was identified in biological samples obtained from patients with membranoproliferative glomerulonephritis (MPGN) and membranous glomerulopathy (MGP). Prostacyclin stimulating factor was identified in four patients (two MPGN patients and two patients with lipoid nephrosis). Mass-spectrogram revealed TACC1 (Transforming, acidic coiled-coil containing protein 2) antioncogene in five patients (three patients with lipoid nephrosis and two MPGN patients). The presence of Integrin alpha-7 indicated high risk of cancer and its relapse. Profilin II protein, which is involved into the actin cytoskeleton remodelling and reparation processes, was found in spectrogram of MGP patients. Filamin A, which is involved in cytoskeleton formation, vascularization and thrombus formation, was found in two out of four MPGN patients. Conclusions: Proteins responsible for inflammation and immune response typical for different stages of pathogenesis are revealed. Each form of chronic glomerulonephritis is characterised by a specific proteomic mirror. This study is noninvasive and perspective for early diagnostics of both inner pathology and particularly renal disorders. The assessed markers are the risk factors present in urine. They allow predicting of therapy efficacy, clinical outcome, chronic renal insufficiency progression rate, and as well as revealing of hidden pathology at early stages.

Эффективность повторных курсов противовирусной и иммунотропной терапии у детей с гематурической формой хронического гломерулонефрита и хронической Эпштейна — Барр вирусной инфекцией

Цель исследования — оценить эффективность повторных курсов противовирусной и иммунотропной терапии у детей с гематурической формой хронического гломерулонефрита (ГФХГН) и сопутствующей хронической Эпштейна — Барр вирусной инфекцией (ЭБВИ). Обследовано 54 ребенка с ГФХГН и хронической ЭБВИ в возрасте 3–17 лет. Больные получали препарат рекомбинантного α-2β-интерферона (ИФН) и препарат, содержащий флавоноиды Deschampsia caespitosa L. и Calamagrostis epiquous L., при наличии признаков активности хронической ЭБВИ дополнительно включали ацикловир. Длительность курса терапии — 3 мес. Количество курсов — 3. Перерыв в лечении между курсами составил три месяца. Эффективность терапии оценивалась путем проведения нефрологического, вирусологического и иммунологического обследования до лечения, через 6 мес., 12 мес. и 18 мес. наблюдения, т.е. через 3 месяца после завершения первого, второго и третьего курсов лечения. Применение повторных курсов противовирусной и иммунотропной терапии у детей с ГФХГН и хронической ЭБВИ привело к уменьшению выраженности эритроцитурии, частоты макрогематурии, тубулярных расстройств, нормализации уровней в сыворотке крови ИФН-α, ИФН-γ, ИЛ-1β и значительному снижению концентрации ИЛ-6. Существенная положительная динамика состояния здоровья детей отмечена после третьего курса терапии, что проявлялось уменьшением респираторной заболеваемости, частоты астенического синдрома, лимфаденопатии, тонзиллита, аденоидита, гепатомегалии, кардиопатии, ликвидацией субфебрилитета, спленомегалии.

1205 Incidence of Acute Post Streptococcal Glomerulonephritis in Children

AimTo present a number of children with set diagnosis of APSGN in the Pristina Children’s Clinic, incidence, clinical characteristics of the disease an treatment. Their follow up aimed to determine...

986 Acute Post Streptococcal Glomerulonephritis in Children

Aim of the study: To present a number of children with set diagnosis of APSGN in the Pristina Children's Clinic, incidence, clinical characteristics of the disease an adequate treatment. Their follow up aimed to determine the further course of the disease and the possibility for progressing into a chronic form. Materials and Methods: This was an analysis of the children treated in the Prishtina Children's Clinic during 2007-2009. The diagnosis of APSGN was set in 132 children based an anamnestic date for existing a prior streptococcal infection, clinical picture, as well as laboratory analyses. Results: The dominant age group was 7-11 year olds, while male patients were more frequent. Anticipatory throat infection appeared in 82% of all cases. In all cases, the clinical symptoms were hematuria and/or proteinuria. Hypertension was present in 73% cases, while edema was confirmed in 79 % of hospitalized patients. Positive ASO was confirmed in 75,8%. All cases were treated successfully and regularly followed up, only 3,5% cases were found resistant to therapy and progressed to chronic form. In all chronic cases, the diagnosis was confirmed after a renal biopsy. Conclusion: In a 96,5% of patient a complete recovery was obtained with further outpatient follow up, and only 3,5 % entered into the form of chronic glomerulonephritis.

Association of HLA-G gene promoter haplotype with childhood IgA nephropathy in the Korean population

Purpose: IgA nephropathy (IgAN) is the most commonly occurring form of chronic glomerulonephritis in pediatric cases. Human leukocyte antigen (HLA) genes have been implicated in various inflammatory and autoimmune diseases. The pre- sent study was conducted to investigate the association between 2 single nucleotide polymorphisms (SNPs) of the HLA-G gene and childhood IgAN. Methods: The authors analyzed and compared HLA-G gene SNPs (rs1736936 and rs2735022) in 174 patients with child- hood IgAN and in 438 healthy controls. In addition, IgAN patients were dichotomized and compared with respect to pro- teinuria ( 4 mg/m 2 /hour), the presence or absence of podocyte foot process effacement, and the presence of pa- thologically early and advanced disease markers such as interstitial fibrosis, tubular atrophy, or global sclerosis. Results :No significant SNP frequency differences were observed for the HLA-G gene between IgAN patients and the con- trol group. Moreover, no significantly associated SNP was observed with the presence of proteinuria, podocyte foot pro- cess effacement, or pathologically advanced markers. However, the haplotype, composed of rs1736936 and rs2735022, showed a significant association with the susceptibility to develop childhood IgAN (haplotype T/C: dominant model, P= 0.049; haplotype C/T: recessive model, P =0.030). Conclusion :Our results indicate that rs1736936 and rs2735022 as the HLA-G gene promoter haplotype might be asso- ciated with the susceptibility to develop childhood IgAN in the Korean population. (Korean J Pediatr 2010;53:548-553)

РЕНИН-АНГИОТЕНЗИН-АЛЬДОСТЕРОНОВАЯ СИСТЕМА ПРИ ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК

THE AIM of the investigation was to specify the role of components of the renin–ngiotensin-aldosterone system (RAAS) in progressing chronic kidney disease, its renal and cardiovascular injuries. PATIENTS AND METHODS. The concentration of plasma aldosterone (CPA), plasma renin activity (PRA), blood serum creatinine (SCr), creatinine clearance (CCr), total renin plasma (TR), inactive plasma renin (IR) were determined in 214 patients with different forms of chronic glomerulonephritis and different stages of chronic kidney disease (CKD).RESULTS. Increased CPA was noted in the progress of CKD, clear inverse nonlinear dependence between CCr and CPA was established. The linear correlation analysis has revealed highly reliable direct correlation between SCr and CPA and confirmed the inverse correlation between CCr and CPA. No relationships were found between the investigated components of RAAS and levels of arterial pressure, although there were correlations of PRA with TR and of IR with TR. A statistically significant feedback was found between PRA and SCr. CONCLUSION. Aldosterone, A II and rennin can be substantial independent factors of the development and progress of renal and cardiovascular complications in patients with CKD.

IgA Nephropathy

IgA Nephropathy

Specific eye fundus lesions in type II membranoproliferative glomerulonephritis

In three adolescents, suffering from membrano-proliferative glomerulonephritis type II, ophthalmoscopy and fluorescein angiography revealed retinal pigment epithelium lesions, referred to as basal laminar drusen. The patient with the longest renal history had the most pronounced fundus changes. These lesions, earlier described in adult patients, are believed to be specific for this particular form of chronic glomerulonephritis.

Long-term prognosis of chronic glomerulonephritis

The dependence of actuarial survival rates on morphological and clinical manifestation of chronic glomerulonephritis (CGN) has been studied in 520 patients followed up for 2-42 years. In grouping the patients along two signs--histological lesion and relapse incidence--the survival in different morphological forms of CGN was found to be similarly dependent on the illness activity. It was high in rare and the lowest in frequent and persisting relapses. Hypertension, high-grade tubulo-interstitial changes and sclerosis over 50 per cent of glomeruli indicate a poor prognosis as signs of severe renal damage under which each relapse may hasten the lethal outcome. Identification of the histological appearance is of high importance in CGN prognosis because of their different manifestations and tendency to relapse.

Secretory immunoglobulin a in urinary tract infection, chronic glomerulonephritis, and renal transplantation

An enzyme-linked immunoassay (ELISA) for the quantitation of secretory IgA (S-IgA) in the urine is described. The assay is sensitive (linear down to 0.02 μg/ml), specific, and reproducible (intraassay variation 7.8%, interassay variation 18.9%). The assay was used to determine the urinary excretion rates of S-IgA in patients with bladder catheter ( n = 12), cystotomy and urinary tract infection ( n = 13), urosepsis ( n = 5), chronic glomerulonephritis, including IgA-nephritis ( n = 31), in renal allograft recipients ( n = 30), and in healthy controls ( n = 46). An elevated S-IgA urinary excretion ( P < 0.01) was found in all patient groups studied. The highest values were observed in urosepsis. No significant differences between S-IgA levels in IgA-nephritis and other forms of chronic glomerulonephritis were detected. The elevated S-IgA excretion in renal allograft recipients indicates that immunosuppressive therapy does not influence the local S-IgA production in the urinary tract. The susceptibility of these patients to urinary tract infections is therefore not due to a S-IgA deficiency.

Changes in lipid metabolism and microcirculation in chronic diffuse glomerulonephritis

Recent studies have shown the frequency of atherosclerosis and its complications in chronic diffuse glomerulonephritis [2, 7]. This disease is often accompanied by a violation of lipid metabolism. It has been shown that all forms of chronic glomerulonephritis (CGN) are characterized by hypercholesterolemia, hyper-b-lipoproteidemia, as well as an increase in total lipids, hypertriglyceridemia [5, 6]. The influence of hyperlipemia on the development of atherosclerosis and its complications, mainly thrombosis, is well known, which also largely depends on microcirculatory disorders.

Evaluation of Recurrent Glomerulonephritis in Kidney Allografts

Abstract The clinical records and biopsy and nephrectomy specimens from 320 patients treated at the Duke University Medical Center between 1965 and 1977 were examined to determine the type and incidence of recurrent glomerulonephritis in the allograft. The diagnosis of recurrent disease required that the histopathologic features of the transplanted kidney resemble those of the diseased native kidney by immunofluorescence and light and electron microscopy. Of 204 patients with tissue available for evaluation from both the native and the transplanted kidney, 117 had some form of chronic glomerulonephritis. Of the 117, there were 61 whose disease could be subclassified further. Idiopathic membranous glomerulonephritis was documented in seven patients, IgA nephropathy in five, focal glomerular sclerosis in 20, type 1 membranoproliferative glomerulonephritis in 16, type 2 membranoproliferative glomerulonephritis in two, proliferative glomerulonephritis in five, crescentic proliferative glomerulonephritis in four and anti-glomerular basement membrane disease in two. In this group of 61, there were 19 patients with 21 allografts in which there was evidence of recurrent glomerulonephritis including four each with idiopathic membranous glomerulonephritis and focal glomerular sclerosis, seven with type 1 membranoproliferative glomerulonephritis, two each with type 2 membranoproliferative glomerulonephritis and anti-glomerular basement membrane disease and one each with IgA nephropathy and crescentic proliferative glomerulonephritis. There were 104 living related donor kidneys grafted into patients with chronic glomerulonephritis, and 78 had tissue available for evaluation. In this group, 15 patients had 16 grafts with recurrent glomerulonephritis. There were 55 cadaveric donor kidneys transplanted into patients with chronic glomerulonephritis, and 39 had tissue available for evaluation. In this group, there were five examples of recurrent glomerulonephritis. Thus, recurrent glomerulonephritis can occur in a variety of histologic subtypes, and in this study population, recurrent glomerulonephritis was more common in allografts from living related donors.

Evaluation of recurrent glomerulonephritis in kidney allografts

The clinical records and biopsy and nephrectomy specimens from 320 patients treated at the Duke University Medical Center between 1965 and 1977 were examined to determine the type and incidence of recurrent glomerulonephritis in the allograft. The diagnosis of recurrent disease required that the histopathologic features of the transplanted kidney resemble those of the diseased native kidney by immunofluorescence and light and electron microscopy. Of 204 patients with tissue available for evaluation from both the native and the transplanted kidney, 117 had some form of chronic glomerulonephritis. Of the 117, there were 61 whose disease could be subclassified further. Idiopathic membranous glomerulonephritis was documented in seven patients, IgA nephropathy in five, focal glomerular sclerosis in 20, type 1 membranoproliferative glomerulonephritis in 16, type 2 membranoproliferative glomerulonephritis in two, proliferative glomerulonephritis in five, crescentic proliferative glomerulonephritis in four and anti-glomerular basement membrane disease in two. In this group of 61, there were 19 patients with 21 allografts in which there was evidence of recurrent glomerulonephritis including four each with idiopathic membranous glomerulonephritis and focal glomerular sclerosis, seven with type 1 membranoproliferative glomerulonephritis, two each with type 2 membranoproliferative glomerulonephritis and anti-glomerular basement membrane disease and one each with IgA nephropathy and crescentic proliferative glomerulonephritis. There were 104 living related donor kidneys grafted into patients with chronic glomerulonephritis, and 78 had tissue available for evaluation. In this group, 15 patients had 16 grafts with recurrent glomerulonephritis. There were 55 cadaveric donor kidneys transplanted into patients with chronic glomerulonephritis, and 39 had tissue available for evaluation. In this group, there were five examples of recurrent glomerulonephritis. Thus, recurrent glomerulonephritis can occur in a variety of histologic subtypes, and in this study population, recurrent glomerulonephritis was more common in allografts from living related donors.

Use of radioimmunoassay for the detection of circulating antistreptococcal antibody in patients with glomerulonephritis.

A method of radioimmunologic quantitation of antibodies to streptococcal antigen separated from the cell wall extract of group A type T12 strain has been developed. The highest values of radioactive antigen binding were observed in acute glomerulonephritis (75%), as compared to chronic glomerulonephritis in which values of 25% to 56% were found depending on the morphology of renal changes. It was shown that none of the patients with pyelonephritis, Alport's syndrome, lupoid nephritis and polycystic renal disease had elevated antistreptococcal antibody levels. In contrast to this, all patients with tonsillitis and proteinuria exhibited increased titre of this antibody. It was shown that the antigen is related neither to M-protein nor to group A polysaccharide and that it is not type-specific because the binding of antigen T12 may be inhibited by the antigen produced from strain T5. Although the antigen is not type-specific, some differences in the response to antigens prepared from various types of streptococci in patients with different forms of chronic glomerulonephritis are observed.

About hypercoagulemia in patients with latent form of chronic glomerulonephritis

The systems of hemostasis and fibrinolysis were studied in 40 patients with latent form of chronic glomerulonephritis. The data obtained indicate the presence of hypercoagulable changes in the hemostasis system in patients.