Subchronic intranasal lipopolysaccharide exposure induces pulmonary autoimmunity and glomerulonephritis in NZBWF1 mice.

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 µg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.

Updates on C3 Glomerulopathy in Kidney Transplantation: Pathogenesis and Treatment Options.

C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement's alternative pathway that leads to the accumulation of the C3 component in the kidney. The disease recurs in more than half of kidney transplant recipients, with a significant impact on graft survival. Recurrence of the primary disease represents the second cause of graft loss after organ rejection. In C3 glomerulopathy, there are several risk factors which can promote a recurrence during transplantation, such as delayed graft function, infection and monoclonal gammopathy. All these events can trigger the alternative complement pathway. In this review, we summarize the impact of C3 glomerulopathy on kidney grafts and present the latest treatment options. The most widely used treatments for the disease include corticosteroids and mycophenolate mofetil, which are already used chronically by kidney transplant recipients; thus, additional treatments for C3 glomerulopathy are required. Currently, several studies using anti-complement drugs (i.e., eculizumab, Ravalizumab, avacopan) for C3 glomerulopathy in kidney transplant patients are ongoing with encouraging results.

Chronological Changes in the Histology of Infection-Related Glomerulonephritis in Renal Allograft: A Case Report.

We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression.

Liver Disease-Associated Glomerulopathies.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect a significant number of individuals globally and their extra-hepatic manifestations, including glomerular disease, are well established. Additionally, liver disease-associated IgA nephropathy is the leading cause of secondary IgA nephropathy with disease course varying from asymptomatic urinary abnormalities to progressive kidney injury. Herein we provide an updated review on the epidemiology, pathogenesis, clinical manifestations, and treatment of HBV- and HCV-related glomerulonephritis as well as IgA nephropathy in patients with liver disease. The most common HBV-related glomerulonephritis is membranous nephropathy, although membranoproliferative glomerulonephritis and podocytopathies have been described. The best described HCV-related glomerulonephritis is cryoglobulinemic glomerulonephritis occurring in about 30% of patients with mixed cryoglobulinemic vasculitis. The mainstay of treatment for HBV-GN and HCV-GN is antiviral therapy, with significant improvement in outcomes since the emergence of the direct-acting antivirals. However, cases with severe pathology and/or a more aggressive disease trajectory can be offered a course of immunosuppression, commonly anti-CD20 therapy, particularly in the case of cryoglobulinemic glomerulonephritis.

Transcription factor Nrf2 activation regulates NETosis, endothelial injury, and kidney disease in myeloperoxidase-positive antineutrophil cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease pathologically characterized by vascular necrosis with inflammation. During AAV development, activated neutrophils produce reactive oxygen species (ROS), leading to the aberrant formation of neutrophil extracellular traps (NETs) via NETosis and subsequent fibrinoid vascular necrosis. Nuclear factor-erythroid 2-related factor 2 (Nrf2) functions as an intracellular defense system to counteract oxidative stress by providing antioxidant properties. Herein, we explored the role of Nrf2 in the pathogenesis of AAV. The role and mechanism of Nrf2 in ANCA-stimulated neutrophils and subsequent endothelial injury were evaluated in vitro using Nrf2 genetic deletion and Nrf2 activator treatment. In corresponding in vivo studies, the role of Nrf2 in ANCA-transfer AAV and spontaneous AAV murine models was examined. Pharmacological activation of Nrf2 in vitro suppressed ANCA-induced NET formation via the inhibition of ROS. In contrast, NET formation was enhanced in Nrf2-deficient neutrophils. Furthermore, Nrf2 activation protected endothelial cells from ANC-induced NETs-mediated injury. In vivo, Nrf2 activation ameliorated glomerulonephritis in two AAV models by upregulating antioxidants and inhibiting ROS-mediated NETs. Furthermore, Nrf2 activation restrained the expansion of splenic immune cells, including T lymphocytes and limited the infiltration of Th17 cells into the kidney. In contrast, Nrf2 genetic deficiency exacerbated vasculitis in a spontaneous AAV model. Thus, the pathophysiological process in AAV may be downregulated by Nrf2 activation, potentially leading to a new therapeutic strategy by regulating NETosis.

Impact of Pretransplant Dialysis Modality on Posttransplant Outcomes: A Single-Center Experience.

OBJECTIVES: It remains unclear whether posttransplant outcomes differ according to the pretransplant dialysis modality (peritoneal dialysis vs hemodialysis). Our aim was to assess posttransplant outcomes in patients with different predialysis modalities. MATERIALS AND METHODS: Two thousand two hundred fifty-eight kidney recipients following up in Hamed Alessa Organ transplant center in Kuwait were included and divided into two groups according to pre-transplant dialysis modality: Group 1: those who received hemodialysis (HD) and group 2: those with peritoneal dialysis (PD). Demographics, pretransplant and posttransplant comorbidities, and patient and graft outcomes were studied. RESULTS: There were 1956 patients on hemodialysis, and 302 patients were on peritoneal dialysis. Most were male patients (1456 vs 802 female patients), with comparable mean age (P = .34). Chronic glomerulonephritis and diabetic nephropathy represented the most common original kidney disease before transplant (27.6% and 21.4%, respectively), with higher prevalence of glomerulonephritis in group 1 and diabetic nephropathy in group 2 (P = .001). The 2 groups were comparable with regard to immunosuppression (induction and maintenance) (P > .05). Posttransplant diabetes and hypertension were significantly higher in the hemodialysis group (P = .004 and P = 003, respectively). There was no significant difference between the 2 groups with regard to the graft outcome (P = .86). However, patient survival was significantly higher in the hemodialysis group (81.2% vs 64.4%). CONCLUSIONS: Compared with peritoneal dialysis, pretransplant hemodialysis is associated with better posttransplant patient survival despite no difference in the graft outcome. Diabetes-related complications could be attributed to such outcomes.

Angiotensin II and post-streptococcal glomerulonephritis.

BACKGROUND: Post-streptococcal glomerulonephritis (PSGN) is a consequence of the infection by group A beta-hemolytic streptococcus. During this infection, various immunological processes generated by streptococcal antigens are triggered, such as the induction of antibodies and immune complexes. This activation of the immune system involves both innate and acquired immunity. The immunological events that occur at the renal level lead to kidney damage with chronic renal failure as well as resolution of the pathological process (in most cases). Angiotensin II (Ang II) is a molecule with vasopressor and pro-inflammatory capacities, being an important factor in various inflammatory processes. During PSGN some events are defined that make Ang II conceivable as a molecule involved in the inflammatory processes during the disease. CONCLUSION: This review is focused on defining which reported events would be related to the presence of this hormone in PSGN.

C3 glomerulopathy in a patient with a history of post-infectious glomerulonephritis.

Post-infectious glomerulonephritis (PIGN) is an immune complex mediated glomerular injury occurring because of an infection, most commonly with group A beta-hemolytic streptococcus in children. C3 glomerulopathy (C3G) is a distinct clinicopathological entity occurring secondary to dysregulation of alternate complement pathway encompassing both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). While most patients with PIGN attain complete remission with normalized complement levels by 6-8 weeks after presentation, patients with C3G continue to have hypocomplementemia with high rates of progressive kidney disease. Here, we report a patient diagnosed with dense deposit disease after his initial presentation with PIGN three years prior. While current literature continues to explore the overlapping and distinguishing features of PIGN and C3G, including how underlying defects in the alternate complement pathway may commonly contribute to both diseases, this case further exemplifies the importance of recognizing the clinico-pathogenic features of PIGN and C3G in pediatric patients with glomerulonephritis.

SARS-CoV-2 infection associated with antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN): a systematic review and two case reports.

BACKGROUND: It has been observed that SARS-CoV-2 infections are associated with the development of various de-novo autoimmune diseases; little is known on new-onset antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) after SARS-CoV-2 infections. METHODS: We conducted a systematic review of previously reported cases with a presumed association of new-onset antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). No language restrictions were applied during the search. The eligible articles included reports of biopsy-proven pauci-immune glomerulonephritis that occurred following SARS-CoV-2 infection. The review was registered in PROSPERO database (CRD42023407786). Two further cases are reported. RESULTS: The mean age of SARS-CoV-2 infection-associated ANCA-GN was 48 ± 19 years. Fifty-six percent of patients showed positivity for myeloperoxidase (MPO)-ANCA. Among tested patients, 36% had concomitantly positive antinuclear antibodies, and 100% had positive rheumatoid factor. Eleven out of the 21 cases (55%) were diagnosed with ANCA-GN during hospitalization due to SARS-CoV-2 infection. The remaining cases were diagnosed after a median of 2.1 months following COVID-19. Seventy-one percent of patients showed improvement in kidney function following different treatments. CASE REPORTS: one patient had positive p-ANCA and cryoglobulin. Another case had positive MPO-ANCA, c-ANCA, cryoglobulinemia, and rheumatoid factor. CONCLUSION: SARS-CoV-2 infection-associated ANCA-GN patients are younger than primary ANCA-GN patients. The presence of atypical ANCA along with co-positivity with other autoantibodies can raise suspicion for SARS-CoV-2 infection-associated ANCA-GN.

Acute interstitial nephritis caused by ANCA-associated vasculitis: a case based review.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points • This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. • The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. • Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). • This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).

Apoptosis in post-streptococcal glomerulonephritis and mechanisms for failed of inflammation resolution.

Post-streptococcal glomerulonephritis is a condition resulting from infection by group A beta-hemolytic streptococcus. The main mechanism involves the formation of immune complexes formed in the circulation or in situ on the glomerular basement membrane, which activates complement and causes various inflammatory processes. Cellular mechanisms have been reported in the induction of kidney damage represented by the infiltration of innate cells (neutrophils and monocyte/macrophages) and adaptive cells (CD4 + lymphocytes and CD8 + lymphocytes) of the immune system. These cells induce kidney damage through various mechanisms. It has been reported that nephritogenic antigens are capable of inducing inflammatory processes early, even before the formation of immune complexes. Usually, this disease progresses towards clinical and renal normalization; however, in a smaller number of patients, it evolves into chronicity and persistent kidney damage. Hypotheses have been proposed regarding the mechanisms underlying this progression to chronicity including failure to induce apoptosis and failure to phagocytose apoptotic cells, allowing these cells to undergo membrane permeabilization and release pro-inflammatory molecules into the environment, thereby perpetuating renal inflammation. Other mechanisms involved include persistent infection, genetic background of the host's complement system, tubulointerstitial changes, and pre-existing kidney damage due to old age and comorbidities.

Evaluation of the significance of complement-related genes mutations in atypical postinfectious glomerulonephritis: a pilot study.

BACKGROUND: Postinfectious glomerulonephritis with C3-dominant glomerular deposition (C3-PIGN) involves C3-dominant glomerular deposition without immunoglobulin. Atypical C3-PIGN involves persistent hypocomplementemia. We investigated the clinical features and explored complement-related gene mutations in atypical PIGN patients. METHODS: We enrolled atypical C3-PIGN patients and collected data regarding the clinical presentation and pathological characteristics and follow-up data. We measured the levels of complement associated antibodies and performed whole-exome sequencing (WES) to detect mutations in complement-related genes. RESULTS: The analysis included six atypical C3-PIGN patients. All patients were antistreptolysin-O (ASO) positive. All patients had varying degrees of hematuria, and four patients had proteinuria. None of the patients were positive for complement-related antibodies. All patients possessed mutations of genes related to the complement pathway, including alternative complement pathway genes-CFI, CFH, CFHR3, CFHR5; the lectin pathway gene-MASP2; and the common complement pathway gene-C8A. The rare variant of CFHR3 has been reported in C3 glomerulonephritis. During 56-73 months of follow-up, the levels of urine markers in three patients recovered within 6 months, and the remaining patients had abnormal urine test results over 12 months. Patients who received glucocorticoid therapy recovered faster. CONCLUSIONS: Our study suggested that complement-related gene mutations may be an important cause of persistent hypocomplementemia in atypical C3-PIGN patients. In addition to variations in alternate pathway-related genes, we also found variations in lectin pathway-related genes, especially MASP2 genes. Although the overall prognosis was good, atypical C3-PIGN patients exhibited a longer period for recovery. Our results suggested that atypical C3-PIGN patients should receive more medical attention and need testing for mutations in complement-related genes.

Biomarkers of histologic severity in children with severe or atypical acute post-streptococcal glomerulonephritis.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is a common cause of acute kidney injury (AKI) in children; however, in a small subgroup, the presentation is one of rapidly progressive glomerulonephritis (RPGN) deteriorating kidney function associated with severe oligo-anuria or a mixed nephritic-nephrotic picture. This study reviewed potential clinical and laboratory factors which may assist the treating clinician to identify patients at high risk of severe disease. METHODS: All kidney biopsies for APSGN performed between 1996 and 2020 were obtained from a departmental biopsy database. Clinical and laboratory data were extracted from the patients' clinical records. Kidney biopsies were reviewed and scored independently by a renal histopathologist. RESULTS: Thirty of 53 (56.6%) patients had stage 3 AKI at initial presentation with a median estimated glomerular filtration rate (eGFR) 27 (IQR 11-41), falling to 20 ml/min/1.73 m2 (IQR 13.3-43) at time of biopsy. Patients who had either a pre-biopsy eGFR < 35 ml/min/1.73 m2 or a ≥ 25% fall in eGFR between admission and biopsy were more likely to have glomerular crescents (p = 0.004). Multivariate regression analysis and receiver operating curve showed the pre-biopsy eGFR most accurately predicted glomerular crescents (p = 0.047, ROC 0.757). There were no significant predictors of nephrotic proteinuria or nephrotic syndrome during the acute phase. CONCLUSIONS: Severe APSGN is associated with a pronounced reduction in eGFR. Calculation of eGFR in this small group of patients may assist in identifying which patient should have an urgent kidney biopsy to facilitate a more accurate clinical diagnosis and management plan.

Infections Following Kidney Transplantation After Exposure to Immunosuppression for Treatment of Glomerulonephritis.

RATIONALE & OBJECTIVE: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation. STUDY DESIGN: Single-center, retrospective cohort study. SETTING & PARTICIPANTS: Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital. EXPOSURE: Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579). OUTCOME: First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial. ANALYTICAL APPROACH: Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status. RESULTS: Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered. LIMITATIONS: Single-center study, no data on methylprednisone use for PTI, unmeasured confounding. CONCLUSIONS: Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary. PLAIN-LANGUAGE SUMMARY: Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant.

[Nephrotic syndrome during pregnancy. Is it chronic glomerulonephritis or preeclampsia? Case report].

Nephrotic syndrome (NS) during pregnancy is a fairly rare pathology and its descriptions in the literature are few. For a long time, NS was associated only with an exacerbation of chronic glomerulonephritis or de novo nephritis, however, the experience of recent years has shown that NS can be a manifestation of the classical obstetric pathology - preeclampsia (PE). The appearance of massive proteinuria with the development of NS is most typical for early PE, which, of course, makes diagnosis difficult, especially if PE develops at an unusually early time (up to 20 weeks). To describe PE that does not fit into the classical criteria, the term "atypical" PE is now used, the development of which can be promoted by both obstetric and somatic risk factors. The presented clinical observation describes the development of early (within 14 weeks) severe PE with the NS at the onset of the disease in a patient with the first multiple pregnancy and complete hydatidiform mole (HM) of one of the fetuses. The progression of nephropathy with the addition of thrombotic microangiopathy and HELLP syndrome made it possible to assume the diagnosis of PE with a high probability. The rapid relief of all clinical manifestations after delivery confirmed this assumption. The role of HM as the main trigger of unusually early PE is discussed. Apparently, the patient's trophoblast disease in the form of hydatidiform mole caused the formation of a severe angiogenic imbalance already in the early stages of pregnancy, which led to the development of PE, which manifested NS as a consequence of podocytopathy due to VEGF deficiency. Thus, the development of NS in a pregnant patient without a history of kidney disease dictates, first of all, the exclusion of PE, until proven otherwise.

De Novo ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis After COVID-19 mRNA Vaccination: A Case Report.

To prevent the spread of the coronavirus disease 2019 (COVID-19) pandemic, vaccines have been authorized for emergency use and implemented worldwide. We present a case of de novo glomerulonephritis (GN) after use of the COVID-19 mRNA vaccine BNT162b2. A 48-year-old man with no relevant medical history was referred for sudden and persistent worsening of renal insufficiency 1.5 months after the second vaccine dose. He had arthralgia and skin rash a week after vaccination. Abdominal pain and diarrhea started 2 weeks later, and he was admitted to the hospital for enteritis treatment. Colonoscopy showed multiple ulcerations and petechiae suggestive of vasculitis in the terminal ileum. After prednisolone therapy, his gastrointestinal symptoms improved, but his renal function continued to deteriorate. Based on kidney biopsy findings and nephrotic-range proteinuria (5,306 mg/24 hours), he was diagnosed with anti-neutrophil cytoplasmic autoantibody (ANCA)-negative pauci-immune crescentic GN (CrGN). He received high-dose steroid pulse therapy and oral cyclophosphamide, and then, gradually underwent steroid tapering, with improvement in proteinuria and renal function over several weeks. Several cases of GN suspected to be related to COVID-19 vaccines have been reported. To our knowledge, this is the first case report of ANCA-negative pauci-immune crescentic CrGN with extrarenal involvement after COVID-19 mRNA vaccination. Our finding expands the spectrum of COVID-19 vaccine-associated GN.

Glomerulonephritis.

Glomerulonephritis (GN) encompasses several disorders that cause glomerular inflammation and injury through an interplay of immune-mediated mechanisms, host characteristics, and environmental triggers, such as infections. GN can manifest solely in the kidney or in the setting of a systemic illness, and presentation can range from chronic and relatively asymptomatic hematuria to fulminant renal failure. Classic acute GN is characterized by hematuria, edema, and hypertension, the latter 2 of which are the consequence of sodium and water retention in the setting of renal impairment. Although presenting signs and symptoms and a compatible clinical history can suggest GN, serologic and urinary testing can further refine the differential diagnosis, and renal biopsy can be used for definitive diagnosis. Treatment of GN can include supportive care, renin-angiotensin-aldosterone system blockade, immunomodulatory therapy, and renal transplant. Prognosis is largely dependent on the underlying cause of GN and can vary from a self-limited course to chronic kidney disease. This review focuses on lupus nephritis, IgA nephropathy, IgA vasculitis, and postinfectious GN.