Infection-related Glomerulonephritis Research Articles

#627 C3 glomerulonephritis and C3-dominant infection related glomerulonephritis—are they similar?

Abstract Background C3 glomerulonephritis (C3GN) and C3 dominant infection related glomerulonephritis (C3-IRGN) comprise two important immune complex mediated diseases. C3GN is caused by dysregulation of the alternate pathway by congenital or acquired abnormalities in the complement pathway. C3-IRGN is often preceded by infection followed by recovery after the infection resolves. Although kidney biopsy findings may be similar in both conditions, the clinical course and treatment differs. We aimed to compare the demographic, clinical and lab parameters of C3GN and C3-IRGN. Methods All kidney biopsies conducted at Institute of Nephrourology, Bengaluru with dominant C3 on immunofluorescence from Jan. 2019-Dec. 2022 were included. The diagnosis of C3-IRGN was established using established criteria. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. Patients with C3GN were treated with steroids and cyclophosphamide, while those with C3-IRGN received antibiotics along with supportive medical management (including renin-angiotensin-aldosterone inhibition). Demographic, clinical and lab parameters were recorded and compared. Results 23 cases of C3-IRGN and 19 cases of C3GN were included in the study. The mean duration of follow-up was 2.79 ± 0.92 years for those with C3GN and 2.78 ± 0.90 years for those with C3-IRGN. C3GN was common in younger patients (second decade of life) while C3-IRGN was common in the fourth and fifth decades of life. C3GN (57.9%) and C3-IRGN (73.9%) were both common in males. Previous infection (26.1% vs 5.3%) and present infection (39.1% vs 15.8%) were significantly more common in C3-IRGN. Hematuria (52.6% vs 34.8%), patient reported “frothy” urine (47.4% vs 21.7%) was significantly more common in C3GN compared to C3-IRGN. 36.8% of patients with C3GN had IFTA of >50% compared to only 8.7% in C3-IRGN. Patients with both conditions most commonly presented with either acute nephritic syndrome or rapidly progressive glomerulonephritis. In contrast, presentation with CKD was significantly more common in C3GN (36.8% vs 0%, P = 0.002) compared to C3-IRGN, and patients with C3GN were more likely to require kidney replacement therapy (47.4% vs 21.7%, P = 0.002). At the end of follow up, 65.2% of patients with C3-IRGN attained complete recovery, compared with only 47.4% of C3GN patients. Conclusion There are characteristic differences between individuals with C3-IRGN and C3GN that may help to better ascertain diagnosis at presentation. Patients with C3GN tend to have worse prognosis, emphasizing the importance of treatments to slow CKD progression and avoid the need for kidney replacement therapy.

Spectrum of Kidney Biopsy Findings Associated With Methamphetamine Use

IntroductionMethamphetamine (METH) is one of the most used drugs of abuse worldwide. However, there are few reports and series examining the toxic kidney effects of METH and associated histopathological changes are not well described. MethodsWe retrospectively identified 112 patients with a history significant for methamphetamine (METH) abuse, of whom 62 were using METH-only and 60 METH + other drugs of abuse. ResultsIn the METH-only cohort, the mean age was 41 years (IQR 33-49) and most were male (76%). Almost all cases (97%) showed evidence of kidney dysfunction at the time of biopsy. 65% had proteinuria, of which 53% were nephrotic-range and 10% had nephrotic syndrome. The most common biopsy diagnosis was acute tubular necrosis (ATN) (66%), of which 19% had myoglobin casts, followed by focal segmental glomerulosclerosis in 53% (NOS in 76% and collapsing in 18%). Biopsy findings also include tubulointerstitial nephritis (37%), thrombotic microangiopathy (24%), and diabetic glomerulosclerosis (DG) (31%).Glomerulonephritis (GN) was identified in one-third of cases, the most common of which were infection-related GN (15%) and IgA nephropathy (11%). 64% of GNs had underlying infection. Of interest, there was increased association for myoglobinuric ATN in those with concurrent ethanol-abuse (p=0.002). Moreover, the METH-only patients were more likely to have DG compared to those with multiple substance-use (p=0.01). More than half demonstrated at least moderate to severe tubulointerstitial scarring and marked hypertensive vascular disease. ConclusionMost patients with METH-use present with acute kidney injury and often have proteinuria associated with a wide spectrum of renal pathology.

Association between Causative Pathogen and Occurrence of Infection-Related Glomerulonephritis in Infective Endocarditis.

Among patients with pathologically-proven infective endocarditis, the association of pathogen with occurrence of infection-related glomerulonephritis (IRGN) was examined in 48 cases of IRGN and 192 propensity score-matched controls. Bartonella was very strongly associated with IRGN (OR 38.2, 95% C.I. 6.7-718.8, p-value <.001); other microorganisms were not.

A rare cause of pregnancy-related acute kidney injury-infective endocarditis-associated infection-related glomerulonephritis

Pregnancy-related acute kidney injury (PRAKI) commonly occurs due to septic abortion and accounts for 15–25% of acute kidney injury (AKI). Glomerulonephritis is a rare cause of PRAKI. The index case was a 20-year-old primigravida who presented in the last trimester of pregnancy with infective endocarditis-associated glomerulonephritis, also complicated by splenic infarct, AKI, and intrauterine fetal death. Renal biopsy revealed crescentic glomerulonephritis and she improved on antibiotic and steroid therapy.

Clinicopathological differences between Bartonella and other bacterial endocarditis-related glomerulonephritis - our experience and a pooled analysis.

Although Staphylococcus aureus is the leading cause of acute infective endocarditis (IE) in adults, Bartonella spp. has concomitantly emerged as the leading cause of "blood culture-negative IE" (BCNE). Pre-disposing factors, clinical presentation and kidney biopsy findings in Bartonella IE-associated glomerulonephritis (GN) show subtle differences and some unique features relative to other bacterial infection-related GNs. We highlight these features along with key diagnostic clues and management approach in Bartonella IE-associated GN. We conducted a pooled analysis of 89 cases of Bartonella IE-associated GN (54 published case reports and case series; 18 published conference abstracts identified using an English literature search of several commonly used literature search modalities); and four unpublished cases from our institution. Bartonella henselae and Bartonella quintana are the most commonly implicated species causing IE in humans. Subacute presentation, affecting damaged native and/or prosthetic heart valves, high titer anti-neutrophil cytoplasmic antibodies (ANCA), mainly proteinase-3 (PR-3) specificity, fastidious nature and lack of positive blood cultures of these Gram-negative bacilli, a higher frequency of focal glomerular crescents compared to other bacterial infection-related GNs are some of the salient features of Bartonella IE-associated GN. C3-dominant, but frequent C1q and IgM immunofluorescence staining is seen on biopsy. A "full-house" immunofluorescence staining pattern is also described but can be seen in IE -associated GN due to other bacteria as well. Non-specific generalized symptoms, cytopenia, heart failure and other organ damage due to embolic phenomena are the highlights on clinical presentation needing a multi-disciplinary approach for management. Awareness of the updated modified Duke criteria for IE, a high index of suspicion for underlying infection despite negative microbiologic cultures, history of exposure to animals, particularly infected cats, and use of send-out serologic tests for Bartonella spp. early in the course of management can help in early diagnosis and initiation of appropriate treatment. Diagnosis of IE-associated GN can be challenging particularly with BCNE. The number of Bartonella IE-associated GN cases in a single institution tends to be less than IE due to gram positive cocci, however Bartonella is currently the leading cause of BCNE. We provide a much-needed discussion on this topic.

2411. Association between Causative Pathogen and Occurrence of Infection-Related Glomerulonephritis in Infective Endocarditis

Abstract Background Infection-related glomerulonephritis (IRGN) is an uncommon complication of infective endocarditis (IE). We have noticed that this complication occurs unusually frequently among patients with IE caused by Bartonella spp. The purpose of this study was to investigate the association between causative pathogen and the occurrence of IRGN in patients with IE. Methods This was a retrospective case-control study. Episodes of pathologically-proven IE with a single causative pathogen, among patients admitted from July 1, 2007, through Jan 1, 2022 were identified from the Cleveland Clinic Infective Endocarditis Registry. Those with definite IRGN (proven by renal biopsy) or probable IRGN (hematuria, proteinuria, elevated creatinine, and depleted serum complement levels) were considered case subjects. Four control subjects were selected for each case subject from patients without definite, probable, or possible IRGN (hematuria, proteinuria, elevated creatinine, or hematuria, proteinuria, depleted serum complement levels), by propensity score matching on age, gender, admission year, and IE category (native or prosthetic), using the nearest neighbor method. The association between pathogen and occurrence of IRGN was examined using logistic regression. Results Forty-eight case subjects (IE with IRGN) were matched to 192 control subjects (IE without IRGN). Of the 48 case subjects with IRGN, 17 (35%) had definite IRGN and 13 (27%) had prosthetic valve endocarditis. Bartonella was the causative pathogen in 9 (3.75%) subjects and of these, 8 had IRGN. There was a very strong association between Bartonella being the causative pathogen in IE and the occurrence of IRGN (OR 47.8, 95% C.I. 11.5 – 323.9, p-value &amp;lt; 0.001). A significant association with IRGN was not found for Staphylococcus aureus, viridans group streptococci, Enterococcus, coagulase-negative staphylococci, or fungi. Conclusion Bartonella being the causative pathogen in IE is very strongly associated with the occurrence of IRGN. Acute glomerulonephritis in a person with clinical or echocardiographic features suspicious for IE, and negative blood cultures, should prompt specific testing for the presence of Bartonella infection by blood PCR or serology. Disclosures Leal Herlitz, MD, Chemocentryx: Advisor/Consultant|Novartis: Advisor/Consultant

Infection-Related Glomerulonephritis (IRGN) due to Gordonia Bacteremia in an Immunocompetent Patient with a Femoral Catheter

Infection-Related Glomerulonephritis (IRGN) due to Gordonia Bacteremia in an Immunocompetent Patient with a Femoral Catheter

Non-streptococcal Bacteria as the Leading Cause of Infection-related Glomerulonephritis in Adults

Infection-related glomerulonephritis (IRGN) is a kidney disorder characterized by inflammation of the glomeruli, the kidney's filtering units, triggered by infections elsewhere in the body. Recent data reveal a shift in the United States, with non-streptococcal bacteria emerging as significant causes of IRGN in adults, replacing the historical dominance of streptococcal infections. This condition arises when the body's immune response to an infection deposes immune complexes in the kidney's glomeruli, resulting in inflammation and damage. Factors like the type and virulence of the bacteria, host immune response, and genetic predisposition contribute to its pathogenesis. Non-streptococcal bacterial infections, including staphylococcal and Escherichia coli (E. coli), are now prominent contributors to adult IRGN. This shift in epidemiology may vary over time and by region. Patients with non-streptococcal bacterial IRGN commonly present with acute kidney injury symptoms, such as swelling, hypertension, hematuria, and proteinuria. Diagnosis involves clinical evaluation, laboratory tests, and kidney biopsy to reveal characteristic glomerular changes. Management focuses on treating the underlying infection with targeted antibiotics, controlling inflammation, and providing supportive care. Severe cases may require dialysis until kidney function recovers. This comprehensive narrative review aims to provide an up-to-date perspective on non-streptococcal bacteria as the leading cause of IRGN in adults. It covers epidemiology, etiology, clinical presentation, diagnosis, and treatment. The prognosis varies based on factors such as the underlying infection and promptness of intervention. This evolving landscape underscores the importance of early diagnosis and tailored management to enhance outcomes in changing IRGN epidemiology among adults. Staying vigilant in diagnosing and managing IRGN remains crucial as it presents new challenges and opportunities for improved patient care.

Non-streptococcal Bacteria as the Leading Cause of Infection-related Glomerulonephritis in Adults

Infection-related glomerulonephritis (IRGN) is a kidney disorder characterized by inflammation of the glomeruli, the kidney’s filtering units, triggered by infections elsewhere in the body. Recent data reveal a shift in the United States, with non-streptococcal bacteria emerging as significant causes of IRGN in adults, replacing the historical dominance of streptococcal infections. This condition arises when the body’s immune response to an infection deposes immune complexes in the kidney’s glomeruli, resulting in inflammation and damage. Factors like the type and virulence of the bacteria, host immune response, and genetic predisposition contribute to its pathogenesis. Non-streptococcal bacterial infections, including staphylococcal and Escherichia coli (E. coli), are now prominent contributors to adult IRGN. This shift in epidemiology may vary over time and by region. Patients with non-streptococcal bacterial IRGN commonly present with acute kidney injury symptoms, such as swelling, hypertension, hematuria, and proteinuria. Diagnosis involves clinical evaluation, laboratory tests, and kidney biopsy to reveal characteristic glomerular changes. Management focuses on treating the underlying infection with targeted antibiotics, controlling inflammation, and providing supportive care. Severe cases may require dialysis until kidney function recovers

Non-streptococcal Bacteria as the Leading Cause of Infection-related Glomerulonephritis in Adults

Non-streptococcal Bacteria as the Leading Cause of Infection-related Glomerulonephritis in Adults

Therapeutic efficacy of steroids in severe infection-related glomerulonephritis

Therapeutic efficacy of steroids in severe infection-related glomerulonephritis

Correlation of Red Blood Cell Casts With Renal Dysfunction in Patients With Infection-Related Glomerulonephritis.

Infection-related glomerulonephritis (IRGN) usually manifests as a proliferative immune-complex glomerulonephritis. The degree of renal dysfunction at presentation can vary. Association with histologic features on kidney biopsy remains unknown. To study the correlation between renal function in IRGN at the time of biopsy and the severity of histologic features. Culture-proven IRGN cases at our facility were included and divided based on estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m2. Patients' demographic and pathologic findings were obtained from electronic medical records and kidney biopsy reports. In total, 104 cases were diagnosed with IRGN on biopsy (mean age, 55.6 ± 15.6 years; male, n = 79 [76%]; median eGFR, 14.5 mL/min/1.73 m2), and 51 of 104 showed eGFR <15 mL/min/1.73 m2. Among all the histologic features assessed, only percent tubules with red blood cell (RBC) casts showed statistical difference, being significantly higher in the lower-eGFR group (P = .004). Multivariable logistic regression analysis also showed that %tubules with RBC casts were associated with lower eGFR (odds ratio, 1.12; 95% CI, 1.01-1.24; P = .01). Patients with 5% or more RBC casts (n = 31) showed a lower eGFR (P = .02) and a higher %cellular crescent (P < .001) compared with those with less than 5% RBC casts. Patients with concomitant anticoagulant therapy (n = 11) showed higher percentages of RBC casts than those without anticoagulants (P = .02). Particular attention to the extent of RBC casts on kidney biopsy is recommended in patients with IRGN because these portend worse renal dysfunction, more so in patients requiring anticoagulation (including for hemodialysis) because they are especially vulnerable to developing anticoagulant-related nephropathy.

Bacterial infection-related glomerulonephritis in patients with diabetes.

Diabetic patients are prone to infections, thus making them a unique cohort at risk of developing bacterial infection-related glomerulonephritis (IRGN). In total, 1693 adult diabetic patients underwent kidney biopsy between 2005 and 2021 at our tertiary care hospital in South India. Of these, 121 consecutive cases which met criteria of bacterial IRGN were included in this study. The mean age of the cohort was 53.1 ± 10.1 years and 83/121 (68.5%) were males. Majority (98.3%) had type 2 diabetes for a median duration of 6 (IQR, 2-12) years. The most common sites of infection were skin (47/121, 38.8%) and urinary tract (15/121, 12.4%). Fifty percent (58/121) of patients had underlying advanced diabetic kidney disease (DKD). Isolated C3 deposits (without immunoglobulin) occurred in 66/121 (54.5%) patients predominantly in advanced DKD patients. IgA-dominant glomerulonephritis occurred in only 9/121 (7.4%) patients. Short-course oral steroid was given to 86/121 (71.1%) patients. Steroid related dysglycemia and immunosuppression related infections occurred in 9/61 (14.8%) and 16/61 (26.2%) patients respectively. Of the 90 patients with follow up details >3 months, 46 (51.1%) progressed to kidney failure over a median period of 0.5 (IQR, 0-7.2) months. Patients diagnosed in the latter half of our study period (2013-2021) were older, less commonly presented with fever, had more pronounced hypocomplementemia and severe renal histology predominantly with a 'starry sky' immunofluorescence pattern. Superimposed bacterial IRGN on underlying DKD is associated with poor renal outcomes. Use of short course steroid was associated with significant toxicity.

#4773 INFECTIVE ENDOCARDITIS COMPLICATED BY RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS: BEYOND ANTIBIOTICS - TO TREAT OR NOT TO TREAT?

Abstract Background A significant proportion of patients with infective endocarditis, present with acute renal failure related to infective endocarditis-associated glomerulonephritis (IEAGN). However, IEAGN differs from other infection-related glomerulonephritis because it may present with clinical and serological disturbances resembling autoimmune diseases such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Its development introduces the dilemma of determining the best treatment approach. Immunosuppressive therapy added to antibiotic treatment may be beneficial for recovery of renal function in some cases of IEAGN with positive ANCA serology, although this approach is still controversial. Case presentation A 32-year-old man presented with fever, fatigue, purpura and rapidly progressive glomerulonephritis. He had a history of atrioventricular septal defect corrected at 9 years of age. Blood analysis showed anemia, acute kidney injury and positive ANCA proteinase 3 (PR3). Urine analysis revealed hematuria and proteinuria. Echocardiogram showed vegetation on the mitral valve with moderate to severe mitral regurgitation. Blood cultures showed Streptococcus mitis. After 14 days of intensive antibiotic regimen, kidney function rapidly deteriorated and ANCA titers remained high. A renal biopsy was performed and showed crescentic necrotizing glomerulonephritis with deposition of C3 and IgM – compatible with infection-related glomerulonephritis. Treatment was initiated with pulses of methylprednisolone, low dose of corticosteroids and intravenous immunoglobulin, combined with antibiotics. Renal function dramatically improved in less than a week. At three months of follow-up, kidney function remains stable and ANCA serology negative. Conclusion In infective endocarditis, ANCA antibodies might have an important pathogenic role rather than secondary phenomena. We suggest that patients with IEAGN, that despite adequate antibiotic regimen present, present with kidney deterioration and evidence of crescentic glomerulonephritis on kidney biopsy, might require addition of immunosuppressives.

Non-Diabetic Renal Diseases in Diabetic Patients with Emphasis on Infection-Related Glomerulonephritis

ABSTRACT Background: Non -diabetic renal diseases (NDRDs) in diabetics are treatable and therefore have better prognosis. Infection-related glomerulonephritis (IRGN) is being frequently reported as NDRD. Objective: We attempt to study the clinicopathologic spectrum of diabetic patients with biopsy proven IRGN. Materials and Methods: This was a retrospective analysis of renal biopsies performed in diabetic patients from January 2014 to June 2021. Demographic data, clinical features, and other laboratory findings were collected. The renal biopsies were classified into diabetic nephropathy (DN) and NDRD. The patients with diagnosis of IRGN were studied in detail. Results: Of the 1972 renal biopsies done in diabetic patients, 537 were NDRD and 1233 were DN. The commonest NDRD was tubulo-interstitial nephritis (n = 173) followed by IRGN (n = 74). The IRGN cases were in the age range of 5-78 years (median-53.5) with M: F = 3.4:1. The median duration of diabetes was six years, with median HbA1c = 7.5. Proteinuria ranged from 0.041 to 13 g/day (median = 1.95) with median serum creatinine of 3.7 mg%. History of preceding infection was present in nine cases. These patients presented with rapidly progressive renal failure (RPRF, 17), nephritic syndrome (27), nephrotic syndrome (27), and asymptomatic proteinuria (3). Median C3-level was 47 mg/dl. The biopsies showed classic endocapillary hypercellularity with neutrophils in mesangium, 45 cases had associated DN. Immunofluorescence performed in 54 cases showed coarse granular deposits of C3C. Conclusions: IRGN should be kept in mind in diabetic patients presenting with RPRF or nephrotic proteinuria. The biopsy and immunofluorescence helps in accurate diagnosis.

The five types of glomerulonephritis classified by pathogenesis, activity and chronicity (GN-AC).

Glomerulonephritis (GN) is a diverse group of immune-mediated disorders. Currently, GN is classified largely by histological patterns that are difficult to understand and teach, and most importantly, do not indicate treatment choices. Indeed, altered systemic immunity is the primary pathogenic process and the key therapeutic target in GN. Here, we apply a conceptual framework of immune-mediated disorders to GN guided by immunopathogenesis and hence immunophenotyping: (i) infection-related GN require pathogen identification and control; (ii) autoimmunity-related GN, defined by presence of autoantibodies and (iii) alloimmunity-related GN in transplant recipients both require the suppression of adaptive immunity in lymphoid organs and bone marrow; (iv) autoinflammation-related GN, e.g. inborn errors of immunity diagnosed by genetic testing, requires suppression of single cytokine or complement pathways; and (v) Monoclonal gammopathy-related GN requires B or plasma cell clone-directed therapy. A new GN classification should include disease category, immunological activity to tailor the use of the increasing number of immunomodulatory drugs, and chronicity to trigger standard chronic kidney disease care including the evolving spectrum of cardio-renoprotective drugs. Certain biomarkers allow diagnosis and the assessment of immunological activity and disease chronicity without kidney biopsy. The use of these five GN categories and a therapy-focused GN classification is likely to overcome some of the existing hurdles in GN research, management and teaching by reflecting disease pathogenesis and guiding the therapeutic approach.

Clinico-Pathogenic Similarities and Differences between Infection-Related Glomerulonephritis and C3 Glomerulopathy.

Recently, the comprehensive concept of "infection-related glomerulonephritis (IRGN)" has replaced that of postinfectious glomerulonephritis (PIGN) because of the diverse infection patterns, epidemiology, clinical features, and pathogenesis. In addition to evidence of infection, hypocomplementemia particularly depresses serum complement 3 (C3), with endocapillary proliferative and exudative GN developing into membranoproliferative glomerulonephritis (MPGN); also, C3-dominant or co-dominant glomerular immunofluorescence staining is central for diagnosing IRGN. Moreover, nephritis-associated plasmin receptor (NAPlr), originally isolated from the cytoplasmic fraction of group A Streptococci, is vital as an essential inducer of C3-dominant glomerular injury and is a key diagnostic biomarker for IRGN. Meanwhile, "C3 glomerulopathy (C3G)", also showing a histological pattern of MPGN due to acquired or genetic dysregulation of the complement alternative pathway (AP), mimics C3-dominant IRGN. Initially, C3G was characterized by intensive "isolated C3" deposition on glomeruli. However, updated definitions allow for glomerular deposition of other complement factors or immunoglobulins if C3 positivity is dominant and at least two orders of magnitude greater than any other immunoreactant, which makes it challenging to quickly distinguish pathomorphological findings between IRGN and C3G. As for NAPlr, it was demonstrated to induce complement AP activation directly in vitro, and it aggravates glomerular injury in the development of IRGN. A recent report identified anti-factor B autoantibodies as a contributing factor for complement AP activation in pediatric patients with PIGN. Moreover, C3G with glomerular NAPlr deposition without evidence of infection was reported. Taken together, the clinico-pathogenic features of IRGN overlap considerably with those of C3G. In this review, similarities and differences between the two diseases are highlighted.

CLINICOPATHOLOGICAL PROFILE AND OUTCOME OF INFECTION-RELATED GLOMERULONEPHRITIS (IRGN):A SINGLE CENTER EXPERIENCE

Infection: related glomerulonephritis (IRGN) is an immunological renal injury due to current or recent infections. With the changing face of IRGN over the years, renal biopsy has attained an important role in diagnosing and differentiating this disease from others as well as prognosticating the long-term outcomes. Materials and Methods: This prospective study conducted in a tertiary health care center in south India includes patients with biopsy proven IRGN who presented between October 2017 to august 2019 and their outcomes at 6 months were analyzed. Results: All the patients whose kidney biopsy was suggestive of IRGN were included. Of the 105 patients suspected and screened, eighty two (82) patients were proved to have IRGN. Mean age of presentation was 49.6 years with slight male preponderance (male 43, female 39). About 31.8 % (26) of patients had diabetes. The skin was the most common site of infection 39% (32) followed by respiratory tract infection 22% (18). Hypocomplementemia was present in 90% of patients. Nephrotic range proteinuria was seen in 54.9% (45) cases. About 4.8% cases were proven to have IgA dominant IRGN. 69.5 % (57) of patients had renal failure at presentation, among them 28% (16) required renal replacement therapy. Complete renal recovery was seen in 67% (55) of patients, 14.09% (11) of the patients progressed to chronic kidney disease at 6 months of follow-up and 9.75% (8) of patients reached end-stage renal disease. Oral steroids were given in 37.8 % (31). Around 10.75% (9) patients had persistent proteinuria despite normal renal function. IRGN in adults may no longer be considered as a glomerular disease with favorable outcome and significant number of patients (23.75%) progress to chronicity following this disease.

Targeted Transcriptional Analysis of IgA Vasculitis, IgA Nephropathy, and IgA-Dominant Infection-Related Glomerulonephritis Reveals Both Distinct and Overlapping Immune Signatures.

IgA vasculitis (IgAV), IgA nephropathy (IgAN), and IgA-dominant infection-related glomerulonephritis (IgA-IRGN) have shared histopathologic features but differences in clinical management and prognosis. The most serious IgAV organ involvement is in the kidneys (IgAV nephritis). In this study, we hypothesized that targeted immune transcript profiling could aid in 1) predicting development of IgAV nephritis in patients with cutaneous IgAV, and 2) differentiating IgAN, IgAV, and IgA-IRGN. RNA was extracted from 24 formalin-fixed paraffin-embedded tissue specimens (16 kidney, 8 skin) from 21 patients with IgAV nephritis (n=7), IgAN (n=5), and IgA-IRGN (n=4), and IgAV skin biopsies from patients with (n=3) and without (n=5) IgAV nephritis. Differential gene expression and gene set enrichment analysis were performed on a total of 594 transcripts (Nanostring immunology panel) profiled using the nCounter system. Skin biopsies in IgAV patients who develop kidney involvement exhibit reduced S100A8/S100A9, IL9, and KIR expression. The kidney tissue immune transcriptomes of IgAN, IgAV, and IgA-IRGN are largely overlapping. IgA-IRGN kidney biopsies are, however, uniquely enriched for transcripts involved in granulocyte chemotaxis. This study identifies immune transcript signatures that may predict IgAV nephritis in skin biopsies and distinguish IgA-IRGN from IgAN and IgAV in kidney biopsies.

Proteomic Analysis of Complement Proteins in Glomerular Diseases

Complement plays an important role in the pathogenesis of glomerulonephritis (GN). Even though the underlying etiology of GN might be different, complement activation with subsequent glomerular deposition of complement proteins result in glomerular injury and progression of the lesions. Routine immunofluorescence microscopy (IF) includes staining for only complement factors C3c and C1q. Therefore, with regard to evaluation of the complement pathways, routine kidney biopsy provides only limited information. In this study, using laser microdissection of glomeruli followed by mass spectrometry, complement proteins and pathways involved in GN were analyzed. We found that C3 followed by C9 are the most abundant complement proteins in GN, indicating activation of classical or lectin or alternative, and terminal pathways, either exclusively or in a combination of pathways. Furthermore, depending on the type of GN, C4A and/or C4B were also present. Therefore, membranous nephropathy (MN), fibrillary GN, and infection-related GN showed C4A dominant pathways, whereas lupus nephritis (LN), proliferative GN with monoclonal Ig deposits, monoclonal Ig deposition disease (MIDD), and immunotactoid glomerulopathy showed C4B dominant pathways. Significant deposition of complement regulatory proteins, factor H-related protein-1 (FHR-1) and factor H-related protein-5 (FHR-5), were also detected in most GN. This study shows accumulation of specific complement proteins in GN. The complement pathways, complement proteins, and the amount of complement protein deposition are variable in different types of GN. Selective targeting of complement pathways may be a novel option in the treatment of GN.