Outcome Of Glomerulonephritis Research Articles

The Clinicopathological Correlation and Outcome of Glomerulonephritis With Crescent: A Single-Center Study.

There is a lack of standardized treatments for patients with less than 50% crescents observed in their renal biopsies. This study aimed to analyze the crescent percentage, clinicopathological characteristics, and renal prognosis of glomerulonephritis (GN) cases with at least one crescentic lesion. This retrospective cohort study was conducted at the Indira Gandhi Institute of Medical Sciences, Patna, from January 2016 to December 2020. Consecutive patients (aged between 18 and 65 years) with renal biopsy findings suggestive of GN and at least one crescent were included in the study. Demographic details and clinical presentation were collected from the medical records. A total of 145 patients were included. The mean (standard deviation (SD)) age was 33.06 (11.739) years. Hemoptysis was significantly higher in the ≥50% crescentgroup (P=0.011). Rapidly progressive glomerulonephritis (RPGN) was significantly higher in the ≥50% crescent group (P<0.001). There was a significant difference observed in mean creatinine (P=0.001), mean crescents (P<0.001), and mean urine polymerase chain reaction (PCR) (P=0.031). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was significantly higher in the ≥50% crescent group (P<0.001). Complete remission decreased as crescents increased. In GN with crescent, the presence of fibrous crescents (≥50%) is associated with a higher rate of treatment resistance (100%) compared to fibrocellular (58.33%) and cellular crescents (6.25%).In the ≥50% crescentgroup, death was significantly higher in patients with fibrous crescentage (57.14%). Crescentpercentage and crescentage were found to be significantly related to greater risk of renal failure and resistance to treatment.

Advancing Treatments for Rare Renal Diseases: New Hopes and Opportunities to Address a High Unmet Need.

The etiology of chronic kidney disease (CKD) is varied and complex. Diabetes and hypertension comprise 2/3 of cases and rare conditions, including inherited genetic diseases, comprise 1/3. We previously reported a 54% increase in clinical studies in CKD in the last 10 years. Hypothesizing a greater increase in rare renal disease studies, we undertook further analysis of metadata from Clinicaltrials.gov. CT.gov was searched for 49 conditions determined to be rare renal diseases posted between Jan-2003 and Dec-2022. Studies were divided into 2 time periods: P1 (2003-2012) and P2 (2013-2022) and analyzed by study type, phase, indication, primary endpoint, population, and funding. Studies increased significantly in P2 versus P1 (123%, p < 0.001) with the greatest rise in observational studies (283%, p < 0.001). Interventional studies increased 93% (p < 0.01), with the greatest rise in early phases (205%, p < 0.001). The most frequent indications were LN, ADPKD, and IgA nephropathy; all increased 77-166% in P2 (p < 0.05 - p < 0.001). Proteinuria was the most frequent primary endpoint, which increased 63% (p = 0.054). Studies with pediatric populations increased 78% (p < 0.01). Most studies were nonindustry funded; however, industry-funded studies increased by 225% (p < 0.001). Clinical research in rare renal diseases has increased significantly in the last 10 years, particularly in glomerular diseases (GDs) and ADPKD. Proteinuria correlates with outcomes in GD, which explains the high percentage of studies with this primary endpoint. Rare renal diseases disproportionately affect children and the rise in studies with pediatric populations is encouraging. The rise in observational studies may signal an increased focus on understanding the natural course and pathophysiology of disease, which may lead to new potential therapeutic targets and future interventional studies. The increase in industry-funded studies suggests basic science is translating into industry-sponsored research.

Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children.

BackgroundMembranoproliferative glomerulonephritis (MPGN) is a rare histopathologic pattern of glomerular injury with limited studies in pediatric patients. Characteristics and outcomes of children with MPGN have also remained to be further explored.MethodsWe retrospectively reviewed the clinicopathological features, genetic findings, treatments and outcomes in 17 pediatric patients pathologically diagnosed with MPGN from 2007 to 2020 in the Children’s National Medical Center in China.ResultsMedian age at disease onset was 9.9 years (IQR, 5.6–11.9 years). Most of the patients (12/17) had nephrotic range of proteinuria, and nephritic-nephrotic syndrome was the most common clinical presentation (35.2%). Secondary causes were identified in eight patients including hepatitis B virus (HBV) infection (n=4), methylmalonic acidemia (MMA, n=2), rheumatoid arthritis (RA, n=1) and Aymé-Gripp Syndrome (n=1). The nine patients with primary MPGN were further identified as immune-complex mediated MPGN (n=8), and unclassifiable MPGN (U-MGPN, n=1). Genetic analyses identified pathogenic variants of MMACHC gene in two cases of MMA and established the diagnosis for Aymé-Gripp syndrome in one case with a de novo variant of MAF gene. Comparing study between the complete or partial remission group (n=8) and non-response group (n=9) showed a significant difference in the timing of renal biopsy (P<0.05). Normal renal function was preserved in ten patients at the last follow-up. Two patients developed into end-stage renal disease (ESRD).ConclusionsChildren with MPGN pattern present heterogenous clinical features. Genetic detection helps to explore underlying causes of MPGN. Early identification of the primary or secondary causes of MPGN in children is vital.

Determining of cytokine levels in the urine in clinical practice.

The paper presents data on the study of the content of cytokines (IL-1β, RAIL-1β, IL-2, IL-4, IL-10, IL-17A, TNF-, IFN-γ) in the morning urine using enzyme immunoassay in healthy individuals (n = 20) and in patients with acute glomerulonephritis (n = 93). The determination of cytokine levels in patients was carried out in the debut of the disease and 12 months after the onset of the disease. The obtained indicators of cytokine content in the urine are presented as absolute values in pg/ml and creatinine-normalized values calculated by the formula: cytokine level (pg/ml) / urine creatinine (µmol/ml). The study was made of changes in the content of cytokines in the urine of patients with glomerulonephritis with respect to a group of healthy individuals, as well as the dynamics of the content of cytokines in the urine during the 12-month observation period. The results of the study showed that the absolute values of cytokines in urine can distort the true picture of the cytokine profile of urine in renal pathology. Normalized values of the predominant number of pro- and anti-inflammatory cytokines (IL-1β, IL-2, IL-8, IL-10, IL-17A and TNF-α) in patients with glomerulonephritis were significantly higher than the corresponding indicators of healthy individuals. The normalized values of cytokines were shown to be as more sensitive indicators than absolute values in the course of analyzing differences in the cytokine profile in patients with glomerulonephritis, depending on chronic and acute course of the disease. These indicators influenced the outcome of glomerulonephritis, assessed, as a rule, 12 months after the onset of the disease. Thus, the low levels of IL-1β, IL-8 and IL-17А detected in the debut of the disease in combination with the high level of RAIL-1β determined the chronization of glomerulonephritis. So, the creatinine-normalized cytokine levels in the urine expand the possibilities of using the evaluation of the cytokine profile of urine to establish changes in the cytokine content in the urine in renal pathology and predict the chronization of glomerulonephritis.

Identifying the ideal metric of proteinuria as a predictor of renal outcome in idiopathic glomerulonephritis

The majority of our insight about glomerulonephritis (GN) is from observational research. Because proteinuria is an important element of outcome in GN, the validity of observational analyses is dependent on the metric used to model proteinuria. Previous metrics of proteinuria included the value at baseline, the average of all values over the entire follow-up (time-averaged), the instantaneous value at each time point (time-varying), or the average of all values prior to each time point, and each of these standardized to body surface area. It was not known which of these metrics best accounts for the risk of renal outcome and should be used in GN research. To address this, we studied 1351 adult patients with IgA nephropathy, focal segmental glomerulosclerosis, and membranous nephropathy from the Toronto GN Registry. Cox regression models for the risk of end-stage renal disease or a halving of estimated glomerular filtration rate included each proteinuria metric and were compared using model fit and discrimination. Proteinuria did not need to be standardized to body surface area. Time-varying proteinuria was the best metric to account for the prognostic effects of proteinuria over time, especially in focal segmental glomerulosclerosis and IgA nephropathy over the majority of follow-up, and in membranous nephropathy earlier in the disease course. Using alternate proteinuria metrics biased analyses up to 30.3%. These findings can improve the validity and design of future observational and prediction modeling studies in GN.

Outcome of glomerulonephritis in live-donor renal transplant recipients: A single-centre experience

ObjectivesTo investigate the frequency and risk factors affecting the incidence of post-transplantation glomerulonephritis (GN) and the impact of GN on the survival of the graft and the patient. Patients and methodsPatients were classified based on histological findings into three groups. Graft survival was ascertained using the Kaplan–Meier method and significance calculated using log-rank tests. For multivariate analysis the Cox model was used. ResultsTransplant glomerulopathy was the most prevalent glomerular disease in our series followed by recurrent GN and lastly de novo GN. In all, 50% of the de novo GN group had diabetes. The worst graft outcomes were in the recurrent GN group (P=0.044). Multivariate analysis revealed ageing of the graft and mammalian target of rapamycin (mTOR) immunosuppression as risk factors for development of GN. While, the age of the recipient and donor, anti-lymphocyte globulin induction therapy, and acute rejection were risk factors for poor graft outcomes. ConclusionsGN is an important issue after transplantation. Tracking the incidence and progression of histological findings in the graft may help to guide proper management and improve graft outcome.

An overview of the British Columbia Glomerulonephritis network and registry: integrating knowledge generation and translation within a single framework

BackgroundGlomerulonephritis (GN) is a group of rare kidney diseases with a substantial health burden and high risk of progression to end-stage renal disease. Research in GN has been limited by poor availability of large comprehensive registries. Substantial variations in access to and administration of treatment and outcomes in GN have been described. Leveraging provincial resources and existing infrastructure, the British Columbia (BC) GN Network is an initiative which serves to combine research and clinical care objectives. The goal of the BC GN Network is to coordinate and improve health care, including robust data capture, on all patients with GN in BC, a Canadian province of over 4.6 million people. This provincial initiative will serve as a model for Canadian or other national and international endeavours.DescriptionThe BC Provincial Renal Agency (BCPRA) is the provincial governmental agency responsible for health delivery for all kidney patients in BC. The BC GN Network has been created by the BCPRA to ensure high quality and equitable access to care for all patients with GN and is a platform for evidence based clinical care programs and associated health policy. All patients with biopsy-proven GN are registered at the time of kidney biopsy into the BCPRA provincial database of kidney disease patients, forming the BC GN Registry. Thereafter, all laboratory results and renal related outcomes are captured automatically. Histology data and core clinical variables are entered into the database. Additional linkages between the GN Registry and administrative databases ensure robust capture of medications, hospital admissions, health care utilization, comorbidities, cancer and cardiac outcomes, and vital statistics.ConclusionsThe BC GN Network and Registry is a unique model in that it combines robust data capture, data linkages, and health care delivery and evaluation into one integrated system. This model utilizes existing health infrastructure to prospectively capture population level data on patients with GN, producing a rich dataset capable of real-time identification and evaluation of GN health policy initiatives, of supporting observational cohort studies and health services research in GN, and of facilitating patient recruitment into GN clinical trials.

Evidence-Based Therapy May Improve Outcome in Glomerulonephritis—A Prospective Field Survey

Introduction and aims: Although glomerulonephritis is rare in the general population it is the second most important cause for end-stage renal failure. The therapy of glomerulonephritis is guided by a limited number of individual clinical trials and treatment recommendations are based on meta-analysis and Cochrane Systematic Reviews. The impact of such therapy standards on the prognosis of glomerulonephritis is not known. Methods: Between October 2002 and December 2008 patients with abnormal urine findings and/or decreasing renal function of unknown cause were referred for renal biopsy. In a collaboration of out-patient nephrologists with a major teaching hospital, all patients received treatment recommendations according to evidence-based therapy guidelines based on Cochrane Systematic Reviews. Patient charts were systematically reviewed and patients were re-examined for follow-up until November 2009. Cox Regression analysis was performed to identify independent prognostic factors. Results: Two hundred patients with primary or secondary glomerulonephritis were identified. Complete follow-up data were available from 196 patients with 324 therapeutic interventions. The mean follow-up was 2.8 ± 2.0 years. Among all patients, 37% remained unchanged ill, 13% died, 17% had progressing renal disease, while 19% had a complete and 14% a partial remission. Proteinuria declined in primary glomerulonephritis (5.0 ± 5.4 g/d to 2.1 ± 3.4 g/d, p Conclusions: In a multivariate model of standardised glomerulonephritis therapy the presence of tubulointerstitial fibrosis was associated with death or progresssive renal disease, while prednisolone-based therapy regimens and intensified nephrological follow-up resulted in a significant delay of endstage-renal failure. This result should direct future health care policies because glomerulonephritis accounts for nearly 20% of the dialysis population.

Glomerulonephritis with Crescents in Children: Etiology and Predictors of Renal Outcome

Objective. To investigate the clinicopathological features and outcome of glomerulonephritis with crescents among Saudi children. Method. This is a retrospective study of cases of crescentic glomerulonephritis (CrGN) seen over a 9-year period. Histological features and renal function were recorded. Results. Thirty-seven cases were enrolled. The mean percent of glomeruli with crescents was 39% (±19). Lupus nephritis (LN) was the commonest etiology (54.1%). At presentation, the serum creatinine (SCr) was 218.2 (±174.3) umol/l, and 57.1% of the cases had nephrotic range proteinuria. By the end of the observation period, SCr dropped to 81.0 (±67.7) umol/l (P = 0.001). Worsening renal function was associated with younger age (P = 0.002), non-LN etiology (P = 0.01), more crescents (P = 0.019), and ATN (P = 0.05). At the end of the followup, more patients in the LN group were dialysis-free (P = 0.017) and had improved renal function (0.01) than in the non-LN group. Using multivariate analysis, the only independent factor found to predict need for dialysis or change in SCr level was percent of globally sclerosed glomeruli (P = 0.034). Conclusion. LN is the main cause of CrGN in our cohort of children. The LN group had less globally sclerorsed glomeruli and better renal prognosis than the non-LN group.

Glomerulonephritis with crescents among adult Saudi patients outcome and its predictors

The aim of this study is to investigate the clinical and pathological features and outcome of glomerulonephritis with crescents among adult patients. This is a retrospective study of all cases of crescentic GN seen over a 9-year period (2001-2010). Histological features were assessed, and renal function at baseline and end of follow-up period was recorded. Results among different etiological groups at baseline and end of follow-up period were compared. The mean age in the whole group was 35.6years (16.2), with the lowest mean in the lupus nephritis (LN) group [27.7years (9.9)] and the highest in the pauciimmune glomerulonephritis (PIGN) group (P=0.001). There were 72 cases enrolled in the study. LN accounted for 49.3% of the cases, PIGN for 26.5%, other immune complex glomerulonephritis (ICGN) for 19% and post-infectious GN accounted for 6.3% The majority (85.7%) of the patients had renal impairment at presentation (mean serum creatinine levels were 247 (85)μmol/l, 412 (75)μmol/l and 230 (141)μmol/l in LN, PICN and ICGN, respectively (P=0.05). Women accounted for 85.3, 76.5 and 36.2% of the patients in LN, PICN and ICGN, respectively (P=0.025). By the end of the follow-up period of 26 (22.9) months, 25.8% of the patients were requiring dialysis (16.70% in the LN group, 50% in PIGN and 25% in ICGN (P=0.05) and 21.7% had nephrotic range proteinuria (16.7, 1 and 33.3%, respectively (P=0.4). Using logistic multivariate analysis, the only independent factors found to predict need for dialysis of prognosis were percent of sclerosed glomeruli (P=0.05) and presence of ATN (P=0.028). Baseline proteinuria or SCr, gender and number of glomeruli with crescents, on the other hand, did not impact prognosis. Using linear regression multivariate analysis, SCr, protein excretion and activity score at biopsy did not influence change in SCr or final SCr during the follow-up period. Using ANOVA to compare the groups of LN, PIGN and ICGN), we found significant differences only in gender between LN and ICGN (P=0.035), in percent glomerular global sclerosis (between LN and PIGN (P=0.007) and between LN and ICGN (P=0.012) and in age (between LN and PIGN (P=0.006). Almost half of our patients with CrGN were due to LN which is higher than that reported by others where PIGN was the more prevalent etiology. Patients with PICN were older and had worse prognosis. This could be explained by the higher number of globally sclerosed glomeruli in the PIGN group.

A Molecular Signature of Proteinuria in Glomerulonephritis

Proteinuria is the most important predictor of outcome in glomerulonephritis and experimental data suggest that the tubular cell response to proteinuria is an important determinant of progressive fibrosis in the kidney. However, it is unclear whether proteinuria is a marker of disease severity or has a direct effect on tubular cells in the kidneys of patients with glomerulonephritis. Accordingly we studied an in vitro model of proteinuria, and identified 231 “albumin-regulated genes” differentially expressed by primary human kidney tubular epithelial cells exposed to albumin. We translated these findings to human disease by studying mRNA levels of these genes in the tubulo-interstitial compartment of kidney biopsies from patients with IgA nephropathy using microarrays. Biopsies from patients with IgAN (n = 25) could be distinguished from those of control subjects (n = 6) based solely upon the expression of these 231 “albumin-regulated genes.” The expression of an 11-transcript subset related to the degree of proteinuria, and this 11-mRNA subset was also sufficient to distinguish biopsies of subjects with IgAN from control biopsies. We tested if these findings could be extrapolated to other proteinuric diseases beyond IgAN and found that all forms of primary glomerulonephritis (n = 33) can be distinguished from controls (n = 21) based solely on the expression levels of these 11 genes derived from our in vitro proteinuria model. Pathway analysis suggests common regulatory elements shared by these 11 transcripts. In conclusion, we have identified an albumin-regulated 11-gene signature shared between all forms of primary glomerulonephritis. Our findings support the hypothesis that albuminuria may directly promote injury in the tubulo-interstitial compartment of the kidney in patients with glomerulonephritis.

Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis

The recognition that human immune responses can be directed by two different subsets of T helper cells (Th1 and Th2) has been an important development in modern immunology. Immune responses polarized by either the Th1 or Th2 subset predominance result in different inflammatory effector pathways and disease outcomes. Many autoimmune diseases are associated with either Th1- or Th2- polarized immune responses. Although these different immune response patterns are relevant to glomerulonephritis (GN), little attention has been paid to the consequences of Th1 or Th2 predominance of nephritogenic immune responses for the pattern and outcome of GN. Unlike other autoimmune conditions, GN results from a variety of different immune responses and has a range of histologic features and immune effectors in glomeruli. This review assesses the data available from studies of experimental and human GN that address the Th1 or Th2 predominance of nephritogenic immune responses and their relevance to the different histopathological patterns and outcomes of GN. In particular, the evidence that Th1-predominant nephritogenic immune responses are associated with severe proliferative and crescentic GN is presented.

Effect of diagnostic delay on disease severity and outcome in glomerulonephritis caused by anti-neutrophil cytoplasmic antibodies.

To measure the time between onset of symptoms and intention to treat in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis; and to investigate the effect of any delay in diagnosis on disease severity at presentation and outcome. All ANCA positive patients with biopsy proven glomerulonephritis presenting in the North West Region over a consecutive period of 57 months were identified from the North West Glomerular Disease Registry. Sixty nine patients were identified and notes from 61 were reviewed. The 61 patients had a median diagnostic delay of 92 days. In only 12 patients had an ANCA test been performed prior to the nephrology referral. Thirty three patients had renal failure requiring dialysis within one week of admission and had a shorter delay (median 72 days) than those not requiring dialysis (median 132 days). None of the 28 patients with independent renal function at presentation required dialysis subsequently. Eighteen (55%) of those who required dialysis recovered independent renal function at three months and 13 (39%) had long term recovery. Both for patients who did and did not undergo dialysis, a longer delay was correlated with an increased percentage of sclerotic glomeruli at presentation. Patients with end stage renal failure had a median delay of 92 days, compared with one of 42 days in those who were dialysis independent at final follow up. Prolonged delay in diagnosis of ANCA associated glomerulonephritis is associated with an increased risk of end stage renal failure.

The Biology of Mesangial Cells in Glomerulonephritis

It is likely that a complex bidirectional interaction occurs between mesangial cells and the immune cells which infiltrate the mesangium during nephritis. Macrophages and other immune cells liberate a series of mediators, including substances such as IL-1, beta-endorphin, TNF, and PDGF--all of which promote the growth of mesangial cells. The end result is mesangial cell proliferation and increased matrix production, both of which are seen in nephritis. The proliferating mesangial cells liberate autocoids such as IL-1 and PDGF, thereby setting up an amplifying loop. Simultaneously, suppressive factors such as TGF-beta are released which antagonize the actions of these growth-promoting substances. The proliferating mesangial cells also produce immunomodulatory peptides, which will in turn act on the infiltrating macrophages to stimulate their replication and activation. Such activated macrophages continue to amplify the inflammatory lesion and also promote the phagocytosis of localized antigen-antibody complexes. The net effect of all of these interactions will depend on the dominance of substances which persist and override the roles of other molecules. Studies of the controls which regulate the production of these growth factors/immune modulators will yield insights into the fundamental mechanisms which determine the outcome in glomerulonephritis.