Intrinsic Kidney Pathology Following COVID-19 Infection in Children and Adolescents: A Systematic Review

Introduction: COVID-19 infections resulting in pathological kidney manifestations have frequently been reported in adults since the onset of the global COVID-19 pandemic in December 2019. Gradually, there have been an increased number of COVID-19-associated intrinsic kidney pathologies in children and adolescents reported as well. The pathophysiological mechanisms between COVID-19 and the onset of kidney pathology are not fully known in children; it remains a challenge to distinguish between intrinsic kidney pathologies that were caused directly by COVID-19 viral invasion, and cases which occurred as a result of multisystem inflammatory syndrome due to the infection. This challenge is made more difficult in children, due to the ethical limitations of performing kidney biopsies to reach a biopsy-proven diagnosis. Although previous systematic reviews have summarized the various pathological kidney manifestations that have occurred in adults following acute COVID-19 infection, such reviews have not yet been published for children and adolescents. We describe the results of a systematic review for intrinsic kidney pathology following COVID-19 infection in children and adolescents. Methods: A systematic literature search of published data up until 31 October was completed through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Research articles reporting new-onset or relapsed intrinsic kidney pathology in children or adolescents (≤18 years) following acute COVID-19 infection were included for qualitative review. COVID-19 infection status was defined by a positive result from a RT-PCR, or nuclear antibody testing. Only full-text articles published in the English language were selected for review. Results: Twenty-nine cases from fifteen articles were included in the qualitative synthesis of this systematic review. Nephrotic syndrome, as an umbrella condition, appeared as the most frequently observed presentation (20 cases) with disease remission noted in all cases with steroid treatment. Other cases included numerous glomerulonephritides, such as acute necrotizing glomerulonephritis, MPO vasculitis and collapsing glomerulopathy, and thrombotic microangiopathies, such as aHUS. For patients with transplanted kidneys, T-cell-mediated rejection and mild tubular interstitial infiltration were noted following testing positive for COVID-19. There were no mortalities reported in any of the included cases, although two patients remained dialysis dependent at hospital discharge. Conclusion: This systematic review highlights the various intrinsic pathological kidney manifestations in children and adolescents as a result of acute COVID-19 infection. The clinical timeline and presentation of these cases support the mechanistic hypothesis between COVID-19 infection and the onset of intrinsic kidney pathologies within this context. The progressive introduction of vaccination programs for children and adolescents may hopefully reduce the severity of COVID-19-associated illnesses, and pathological kidney manifestations in this population.

Microscopic polyangiitis: Modern concepts and treatment options

The article summarizes the modern concepts of microscopic polyangiitis (MPA), a primary ANCA-associated systemic necrotizing vasculitis without immune globulin deposition (pauci-immune) that affects mainly small vessels, while granulomatous inflammation is absent. Necrotizing glomerulonephritis is very common and pulmonary capillaritis often occurs. MPA can cause rapidly progressive damage to organ systems. The modern possibilities of MPA treatment, primarily anti-B cell therapy with rituximab, are discussed.

Complement catalyzing glomerular diseases

Complement is an evolutionarily conserved system which is important in the defense against microorganisms and also in the elimination of modified or necrotic elements of the body. Complement is activated in a cascade type manner and activation and all steps of cascade progression are tightly controlled and regulatory interleaved with many processes of inflammatory machinery. Overshooting of the complement system due to dysregulation can result in the two prototypes of primary complement mediated renal diseases: C3 glomerulopathy and thrombotic microangiopathy. Apart from these, complement also is highly activated in many other inflammatory native kidney diseases, such as membranous nephropathy, ANCA-associated necrotizing glomerulonephritis, and IgA nephropathy. Moreover, it likely plays an important role also in the transplant setting, such as in antibody-mediated rejection or in hematopoietic stem cell transplant associated thrombotic microangiopathy. In this review, these glomerular disorders are discussed with regard to the role of complement in their pathogenesis. The consequential, respective clinical trials for complement inhibitory therapy strategies for these diseases are described.

AB0395 RENAL INVOLVEMENT IN HENOCH-SCHÖNLEIN PURPURA

Background:Henoch-Schönlein purpura (HSP), also known as rheumatic purpura, is an immune complex vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. HSP is more common among children than adults. Kidney damage is the principal prognostic determinant in HSP. The aim of this study is to evaluate the renal manifestations of HSP.Objectives:The aim of this study is to evaluate the renal manifestations of HSP.Methods:This was a retrospective study of 35 patients with diagnosed HSA, who were admitted between the time period may 2008 and november 2018. All of these patients met the American College of Rheumatology classification criteria for a diagnosis of HSP. Renal involvement was defined as the presence of proteinuria or hematuria.Results:The study group consisted of 35 patients, 20 women (57%) and 15 men (43%). The mean age was 48.8± 18.7 years. The incidence rates of skin, joint, gastrointestinal and central nervous system involvement were 91.4, 77.1, 54.2 and 2.8%, respectively. Elevated serum IgA levels occurred in 5.7 %. Six patients (17.1%) were given corticosteroids during the first 3 months of their HSP, which were indicated for severe gastrointestinal (n=5) or renal involvement (n=1). Eighteen of the thirty five patients (51.42%) had renal involvement. There were 12 women and six men. All patients had proteinuria (100%). Hematuria has been identified in 11 patients (61.1%) and renal insufficiency in 4 patients (22.2%). The renal involvement was mainly detected in the first month. Renal biopsy was affected in four patients (22.2%). An endocapillary glomerulonephritis was found in 3 patients and an extra capillary necrotizing glomerulonephritis in one patient. The immunofluorescence showed the presence of IgA deposits in 4 patients.Conclusion:Renal involvement dominates the prognosis for the disease. The most common clinical expression is the association of microscopic hematuria with proteinuria.Disclosure of Interests:None declared

Could COVID-19 Trigger Presentation or Exacerbation of Vasculitides? (A 14-Year-Old Girl with Newly Diagnosed GPA After COVID-19 Infection)

Introduction: Granulomatosis with polyangiitis (GPA) is a kind of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), which involves small-to-medium-sized vessels. Besides, GPA usually involves the upper and lower respiratory tract, and also causes necrotizing glomerulonephritis. The involvement of the heart and gastrointestinal (GI) tract in GPA is unusual, and these are atypical places of this vasculitis. Case Presentation: A 14-year-old girl with a newly diagnosed GPA after afflicting with COVID-19 infection presented with ST-elevation Myocardial Infarction (MI), GI perforation, and intracranial hemorrhage. Conclusions: Although GPA is rare in the pediatric population, it might occur in this age group and could involve multiple organ systems.

Pediatric P-ANCA Vasculitis following COVID-19

Background: Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA), a subset of ANCA, are associated with a multisystem vasculitis affecting small blood vessels in the body. A handful of adult patients who developed vasculitis post-COVID-19 infection have been reported. Although COVID-19 infection has been shown to drive an exaggerated immune response in the pediatric population, such as MIS-C (multisystem inflammatory syndrome in children), only one case of vasculitis following COVID-19 infection has been reported previously in children. Case presentation: Seventeen-year-old male with a past medical history of COVID-19 pneumonia two months prior presented with acute kidney injury/failure and diffuse alveolar hemorrhage (DAH). Rheumatologic workup revealed P-ANCA and Myeloperoxidase (MPO) positivity. Kidney biopsy showed necrotizing glomerulonephritis with limited immune complex deposition. Subsequently, he was treated with pulse steroids, plasmapheresis, and ultimately started on cyclophosphamide. Conclusions: To our knowledge, this report presents the second reported pediatric case of P-ANCA / MPO vasculitis following COVID-19 infection.

ANCA-associated vasculitis overlaps with systemic sclerosis: a case report and literature review

Background Systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) both affect the kidney and may cause renal failure. Treatment of AAV is dramatically different from that of SSc renal crisis (SRC). Kidney biopsy is not recommended for diagnosing SRC, but it is the only reliable diagnostic method for AAV. Case presentation Here, a 49-year-old male patient with diffuse SSc presented with acute renal insufficiency and detectable ANCA with myeloperoxidase-specific antibodies. A renal biopsy revealed necrotizing glomerulonephritis and was consistent with AAV. This finding confirms the existence of AAV and SSc overlap syndrome. The patient was treated with intravenous methylprednisolone, intravenous cyclophosphamide, tandem membrane plasma exchange, and hemodialysis. After treatment, his clinical symptoms remained stable, and his creatinine and C-reactive protein (CRP) levels have remained normalized as of his most recent follow-up after hospital discharge. Conclusions AAV can overlap with SSc; although this condition is rare, it is associated with considerable morbidity and mortality. Therefore, it is critical to recognize AAV in the setting of worsening renal function due to SSs and provide appropriate treatment. Several clinical features are suggestive of AAV rather than SRC, but renal biopsy is required for accurate diagnosis.

Antimyeloperoxidase and proteinase 3 antibodies for nephritis flare prediction in ANCA-associated-vasculitis

Background The value of myeloperoxidase and proteinase 3 antibodies titers in the assessment of renal disease activity and flare prediction in patients with ANCA-associated-vasculitis (AAV) is not well-known. Methods Retrospective study including 113 AVV patients with a renal biopsy-proven pauci-immune necrotizing glomerulonephritis from seven Spanish hospitals. The main inclusion criteria were assessment of MPO antibodies (MPOab) using multiplex flow immunoassay and PR3 antibodies (PR3ab) measurements using immunoassay chemiluminescence with an identical range of values for all participating centers. Results Serum MPOab, 3 ± 1.2 months before relapse, was higher in patients who relapsed (19.2 ± 12.2 vs 3.2 ± 5.1 AI, p < 0.001). The discrimination value of MPOab 3 months before renal relapse had an AUC of 0.82 (95%CI 0.73-0.92; p < 0.001). ΔMPOab (change in antibodies titration 6 months before relapse) was higher in patients who relapsed [8.3 ± 12 vs 0.9 ± 3.1 AI, p = 0.001) (AI; antibody index unit). The discrimination value of ΔMPO had an AUC of 0.76 (95%CI 0.63-0.88; p < 0.001). The positive predictive value of renal relapse in PR3 patients is 100% and the negative predictive value of renal relapse in patients with PR3 positive titers is 57.1%. Serum PR3ab was higher in patients who relapsed 2.8 ± 1.4 months before relapse (58.6 ± 24.6 vs 2.0 ± 0.6 AI, p < 0.001). Conclusions MPO antibody level monitorization using multiplex flow immunoassay and PR3 measurements using immunoassay chemiluminescence are useful and sensitive tools for the prediction of renal relapse in the follow-up of AAV patients with renal disease, and relevant surrogate markers of renal disease activity.