Pauci-immune Glomerulonephritis Research Articles

Prognostic Value of Microscopic Hematuria after Induction of Remission in Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis

Background: Pauci-immune glomerulonephritis (PIGN) is a major prognostic factor in antineutrophil cytoplasmic antibodies-associated vasculitis (AAV). Renal remission is usually defined as improvement or stabilization of serum creatinine and proteinuria levels but the significance of hematuria is unclear. We evaluated the prognostic value of microscopic hematuria in patients in remission from a first flare of PIGN. Methods: A multicenter retrospective study was conducted of all patients with histologically proven PIGN in northern France who presented a first renal flare of AAV between 2003 and 2013. All patients received conventional induction treatment and were considered in remission. Two groups were defined by the presence (H+) or absence (H–) of hematuria (dipstick 1+ and/or cytology ≥10,000 erythrocytes/mL). The primary outcome measure was the occurrence of renal relapse (RR) and/or end-stage renal disease (ESRD). Results: Eighty-six patients were included: 41 (48%) had hematuria at remission. The median follow-up time was 44 ± 34 months. There was no significant difference between the groups in terms of the primary endpoint or the number of RR. However, the survival rate without RR was significantly lower in the H+ group (p = 0.002). In multivariate analysis, risk factors for RR were hematuria at remission for relapses within 44 months (hazard ratio [HR] 4.15; 95% CI 1.15–15.01; p = 0.03) and the duration of maintenance immunosuppressive therapy (HR 0.96 per additional month; 95% CI 0.94–0.99; p = 0.002). Conclusion: Hematuria at remission after a first PIGN flare was not associated with ESRD but with the occurrence of RR within 44 months of remission.

Spectrum of biopsy-proven renal disease in northern India: A single-centre study.

Pattern of kidney diseases varies across geographies due to multiple factors. There is a paucity of information from South Asia due to the absence of nationwide/regional biopsy registries. This study aimed to delineate the spectrum of renal parenchymal diseases in our region. Records of kidney biopsies done in our nephrology department between 2006 and 2016 were analysed. Clinico-pathological correlation was done from the available records. Of the 3275 biopsy evaluated, 61.9% were males, and mean age was 33.2 ± 14.2 years. 6.2% patients were elderly (age ≥ 60 years). Nephrotic syndrome (60.3%) was the commonest indication for biopsy. On histology, 73.0% patients had primary glomerulonephritis (GN), 15.5% secondary GN, 5.3% tubulo-interstitial and 3.7% vascular disease. Focal segmental glomerulosclerosis (FSGS) was the commonest primary GN accounting for 18.2% of all GNs, followed by minimal change disease (16.8%), membranous nephropathy (MN) (16.0%) and IgA nephropathy (10.4%). Lupus nephritis (10.6%) and amyloidosis (3.7%) were the commonest secondary GN. The commonest cause of nephrotic syndrome was minimal change disease (22.9%), acute nephritic syndrome was lupus nephritis (30.6%), rapidly progressive renal failure was pauci-immune crescentic GN (24.5%). IgA nephropathy was the commonest etiology of asymptomatic urinary abnormalities (26.3%) and gross haematuria (50%). About 60.9% patients of undetermined chronic kidney disease had glomerular diseases, and 13.6% had chronic tubulointerstitial nephritis. Lupus nephritis and acute cortical necrosis were significantly more common in females compared with males. This is one of the largest cohorts of kidney biopsies from India, and it delineates the unique features and differences in the pattern of kidney disease in our population.

Gremlin, A Potential Urinary Biomarker of Anca-Associated Crescentic Glomerulonephritis

Gremlin renal overexpression has been reported in diabetic nephropathy, pauci-immune crescentic glomerulonephritis and chronic allograft nephropathy and has been implicated in the pathophysiology of the progression of renal damage. However, it is unknown whether urinary Gremlin can be associated with renal functional status, renal biopsy findings and outcome. To examine these associations we studied 20 patients with ANCA+ renal vasculitis and very high urinary Gremlin (354 ± 76 ug/gCr), 86 patients with other glomerular diseases and moderately elevated urinary Gremlin (83 ± 14 ug/gCr) and 11 healthy controls (urinary Gremlin 11.3 ± 2.4 ug/gCr). Urinary Gremlin was significantly correlated with renal expression of Gremlin (r = 0.64, p = 0.013) observed in cellular glomerular crescents, tubular epithelial cells and interstitial inflammatory cells. Moreover, urinary Gremlin levels were correlated with the number of glomerular crescents (r = 0.53; p < 0.001), renal CD68 positive cells (r = 0.71; p < 0.005), tubulointerstitial fibrosis (r = 0.50; p < 0.05), and serum creatinine levels (r = 0.60; p < 0.001). Interestingly, Gremlin expression was colocalized with CD68, CD163 (monocyte/macrophage markers) and CCL18 positive cells. ROC curve analysis showed that the cutoff value of urinary Gremlin in glomerular diseases as 43 ug/gCr with 72% of sensitivity and 100% of specificity [AUC: 0.96 (CI 95% 0.92–0.99] (p < 0.001). For ANCA+ renal vasculitis the value of urinary Gremlin of 241 ug/gCr had 55% of sensitivity and 100% of specificity [AUC: 0.81 (CI 95% 0.68–0.94) (p < 0.001]. Based on these results we propose that urinary Gremlin represents a non-invasive biomarker in ANCA+ renal vasculitis, and suggest a role of Gremlin in the formation of crescents.

Microscopic polyangiitis associated with thymic tumor: a case report and review of the literature

BackgroundThymic hyperplasia and thymic epithelial tumor (thymoma) have been associated with a variety of autoimmune diseases. Renal involvement has been reported in patients with thymoma. Minimal change disease and membranous nephropathy are frequently observed in glomerular lesions of thymoma patients, but ANCA-associated renal vasculitis is rare. We present a case of thymoma-associated microscopic polyangiitis with positivity for three ANCAs: MPO-ANCA, PR3-ANCA and azurocidin-ANCA.Case presentationAn 89-year-old Japanese woman was admitted to our hospital following an episode of general fatigue, nausea, muscle weakness of the lower limbs, and ophthalmoplegia. On urinalysis, proteinuria, hematuria, and cellular casts were observed. Elevated levels of serum creatinine and C-reactive protein were also demonstrated, and MPO-, PR3- and azurocidin-ANCA were detected on serological examination. Renal biopsy showed pauci-immune crescentic glomerulonephritis. We therefore diagnosed rapidly progressive glomerulonephritis due to microscopic polyangiitis. Acetylcholine-receptor antibody was also detected. Chest computed tomography and MRI revealed a lobulated tumor in the anterior mediastinum. We thus also diagnosed myasthenia gravis with thymoma.ConclusionConsidering the patient’s triple-ANCA positivity, thymic diseases may be associated with the pathogenesis of ANCA-associated vasculitis due to central T-cell tolerance. A further accumulation of cases is needed, because thymectomy does not always induce the remission of thymoma-associated autoimmune diseases.

Predicting long-term renal and patient survival by clinicopathological features in elderly patients undergoing a renal biopsy in a UK cohort.

BackgroundSeveral publications have demonstrated the use of renal biopsy in elderly patients in establishing a diagnosis and enabling directed therapy. However, evidence on the long-term outcomes following biopsies is lacking. The aim of this study is to describe the renal and patient outcomes in elderly patients according to indication for biopsy, clinical parameters and the histological diagnosis.MethodsWe performed a retrospective cohort study of 463 patients >70 years old who underwent a renal biopsy at our centre between 2006 and 2015.ResultsThe median age of the patients was 74.8 (range 70.0–89.6) years. The most frequent primary diagnoses were pauci-immune crescentic glomerulonephritis (GN; 12%), acute interstitial nephritis (10.8%) and membranous GN (7.1%). Death-censored renal survival at 1 and 5 years following the index biopsy was 85.2 and 75.9%, respectively, and patient survival at 1 and 5 years was 92.2 and 71.6%, respectively. Patients who progressed to end-stage renal disease (ESRD) were at higher risk of dying compared with patients who did not require dialysis [hazard ratio 2.41 (95% confidence interval 1.58–3.68; P < 0.001]. On multivariate analysis, factors associated with the risk of progression to ESRD were creatinine (P < 0.001), heavy proteinuria (P = 0.002) and a non-chronic kidney disease (CKD) biopsy indication (P = 0.006). A histological diagnosis of primary GN (P = 0.001) or tubulointerstitial nephritis (P = 0.008) was associated with a favourable renal outcome, while patients with vasculitis and paraprotein-related renal disease (PPRD) had the highest risk of requiring dialysis (P = 0.0002 and P = 0.003, respectively). PPRD was also an independent risk factor for death.ConclusionsThis study demonstrates that renal biopsies in the elderly not only enable directed therapy, but also provide prognostic information on renal and patient survival.

Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience

Rationale & ObjectiveThe approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects.Study design, setting, & participantsWe retrospectively reviewed all cancer patients from 2008 to 2018 who were treated with a CPI and subsequently underwent a kidney biopsy at The University of Texas MD Anderson Cancer Center.ResultsWe identified 16 cases diagnosed with advanced solid or hematologic malignancy; 12 patients were male, and the median age was 64 (range 38 to 77 years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14 weeks (range 6–56 weeks). The average time from AKI diagnosis to obtaining renal biopsy was 16 days (range from 1 to 46 days). Fifteen cases occurred post anti-PD-1based therapy. ATIN was the most common pathologic finding on biopsy (14 of 16) and presented in almost all cases as either the major microscopic finding or as a mild form of interstitial inflammation in association with other glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 cases. Steroids and further immunosuppression were used in most cases as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving complete to partial renal recovery.ConclusionsOur data demonstrate that CPI related AKI occurs relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most common pathological finding; however it can frequently co-occur with other glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI.

The role of mammalian target of rapamycin pathway in the pathogenesis of pauci-immune glomerulonephritis

Background: The characteristic lesion of pauci-immune glomerulonephritis is focal necrotizing and crescentic glomerulonephritis. The underlying mechanisms in the formation or progression of crescent formation need further investigations. Therefore, we aimed to evaluate the role of mammalian target of rapamycin (mTOR), which might be a potential therapeutic target, in kidney biopsies of patients with pauci-immune glomerulonephritis.Methods: The patients diagnosed as pauci-immune glomerulonephritis at an outpatient nephrology clinic were retrospectively reviewed and those patients who had a kidney biopsy before receiving an immunosuppressive treatment were included in the study. Kidney biopsy specimens were immunohistochemically stained with mTOR, antibodies of phosphatase and tensin homolog (PTEN) and transforming growth factor-β (TGF-β) and scored by an experienced renal pathologist.Results: In total, 54 patients with pauci-immune glomerulonephritis (28 [52%] female) were included. According to the histopathologic examination, 22% of our cases were classified as focal, 33% crescentic, 22% mixed, and 22% as sclerotic. The mTOR was expressed in substantial percentages of glomeruli of patients with pauci-immune glomerulonephritis. However, we observed PTEN expression in all samples and mTOR in all tubulointerstitial areas. mTOR expression was found to be related with the presence of crescentic and sclerotic changes observed in glomeruli and the degree of fibrosis in interstitial areas. Serum creatinine level or response to treatment was not found to be associated with mTOR pathway expression.Conclusion: Our results suggest that mTOR pathway may play role in the pathogenesis of pauci-immune glomerulonephritis, besides targeting this signaling may be an alternative option for those patients.

Association between neutrophil-lymphocyte & platelet lymphocyte ratios with prognosis & mortality in rapidly progressive glomerulonephritis.

Background & objectives:Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome manifested by features of nephritic syndrome and progressive loss of renal function over a short time. The objective of this study was to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic factors and pathological findings of renal biopsy in RPGN.Methods:Consecutive newly diagnosed RPGN patients who had follow up for at least six months were retrospectively analyzed. The estimated glomerular filtration rate (eGFR) was calculated. Albumin, C-reactive protein (CRP) levels and CRP/albumin ratio were also calculated.Results:Fifty four patients were included in the study. The mean age was 48.92±20.12 years. Clinicopathological diagnosis was pauci-immune glomerulonephritis (GN) in 40 while two had postinfectious GN, six systemic lupus erythematosus, three IgA nephropathy, two Henoch-Schönlein purpura and one membranoproliferative GN. The mean NLR was 7.02±6.34 and mean PLR was 273.90±39.15. Positive correlations between NLR and CRP levels (P=0.009, r=0.511) and CRP/albumin ratios (P=0.005, r=0.542) were observed. PLR and CRP/albumin ratios (P=0.041, r=0.412) were correlated positively. The per cent of fibrocellular crescents was negatively correlated with NLR (P=0.019, r=−0.291), and positively correlated with the lymphocyte count (P=0.05, r=0.256). In secondary crescentic subgroup, the per cent of fibrinoid necrosis had a positive correlation with PLR (P=0.013, r=0.642). Both NLR (P=0.036) and PLR (P=0.051) detected at the first month of the treatment period, were observed to be significantly correlated with mortality.Interpretation & conclusions:This study showed that NLR could predict mortality in patients with RPGN; correlated with systemic inflammation; showed a negative correlation with the per cent of fibrocellular crescents and could be regarded as a measure of glomerular inflammatory state. Moreover, PLR may be considered to be an indicator of disease severity in acute phase of crescentic GN.

A rare case of Alport syndrome, atypical hemolytic uremic syndrome and Pauci-immune crescentic glomerulonephritis

BackgroundRenal thrombotic microangiopathy (TMA) is occasionally seen in biopsies with pauci-immune necrotizing crescentic glomerulonephritis (PCGN). Recent study indicated that the complement activation is more prominent in the ANCA-negative glomerulonephritis.Case presentationWe report a case of concurrent TMA and PCGN without ANCA positivity. Interestingly, our patient also had biopsy features supportive of Alport syndrome (AS). Genetic studies identified variants and polymorphisms in alternative complement pathway genes that confer substantial risk of developing atypical hemolytic uremic syndrome (aHUS).ConclusionsAbnormal activation in complement pathway may represent a common pathogenic link between these three distinct entities.

Малоиммунный гломерулонефрит с полулуниями: клинико-морфологический и прогностический анализ

Малоиммунный гломерулонефрит с полулуниями: клинико-морфологический и прогностический анализ

Case report: de novo ANCA-associated vasculitis after kidney transplantation treated with rituximab and plasma exchange

BackgroundAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis causes end-stage renal failure in up to a third of cases even with treatment. The disease recurs occasionally after kidney transplantation, but new onset of ANCA-associated vasculitis after transplantation is highly unusual. The use of rituximab or plasmapheresis for de novo disease after transplantation has not previously been reported.Case presentationRoutine post-transplant follow-up for a 66-year old asymptomatic woman revealed a rise in creatinine from 1.8 to 2.6 mg/dl and increased proteinuria. She had received a cadaveric kidney transplant 20 months previously for end-stage autosomal dominant polycystic kidney disease. Renal allograft biopsy unexpectedly demonstrated pauci-immune glomerulonephritis with extracapillary proliferation and interstitial inflammation. Concurrent serum tested strongly positive for ANCA specific to proteinase 3 (PR3), but stored pre- and post-transplantation serum samples tested negative. These findings established a diagnosis of de novo ANCA-associated vasculitis in the renal allograft.We started treatment with high-dose corticosteroid and rituximab. Despite this, serum creatinine continued to rise and glomerulonephritis remained active in a repeat biopsy. Escalation of the treatment with seven sessions of plasmapheresis led to a temporary improvement in creatinine. No further features of vasculitis emerged and PR3-ANCA titres declined. However, multiple infections complicated the recovery period and were associated with progressive loss of renal transplant function. Four months after the index presentation, transplant function became insufficient and dialysis was restarted.ConclusionsDe novo ANCA-associated vasculitis after renal transplantation is exceptionally rare. It poses a significant risk to graft survival even in the context of intensified immunosuppression. Management relies on clinical evidence from populations with native renal function, yet post-transplant patients may be at increased risk of treatment-related adverse events. Precautions against these risks are crucial in the delivery of care.

Clinical and pathologic characteristics of pauci-immune anti-myeloperoxidase antibody associated glomerulonephritis with nephrotic range proteinuria

Background: Heavy proteinuria in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is usually considered to be associated with immune deposits in renal biopsy. Nephrotic ANCA GN without immune deposits (pauci-immune) is rare and has not been studied specially. In this study characteristics of these patients are to be investigated. Methods: Clinical and pathological characteristics from 20 kidney biopsy-proven pauci-immune anti-myeloperoxidase antibody-associated GN patients with nephrotic proteinuria were analyzed and were compared with ANCA GN patients without nephrotic proteinuria. Results: Acute kidney injury (AKI) and gross hematuria were much prevalent but extra-renal involvement was less prevalent in pauci-immune ANCA GN with nephrotic proteinuria than in pauci-immune ANCA GN without nephrotic proteinuria. No more severe hypoalbuminemia, hypercoagulability, hyperlipidemia or higher thrombosis incidence were found between two groups. Compared with patients without nephrotic proteinuria, patients with nephrotic proteinuria had more prevalent crescentic category in histopathology. Proteinuria decreased quickly after treatment but much poorer renal prognosis was found in pauci-immune ANCA GN with nephrotic proteinuria. The results of urinary albumin to total protein ratio and urinary protein electrophoresis showed pauci-immune ANCA GN with nephrotic proteinuria had obvious non-selective proteinuria. Conclusions: Pauci-immune ANCA GN with nephrotic proteinuria do not have more severe hypoalbuminemia, hypercoagulability or hyperlipidemia than patients without nephrotic proteinuria. Non-selective proteinuria might be the reason. However, pauci-immune ANCA GN with nephrotic proteinuria have more prevalent crescentic category in histopathology, higher incidence of AKI, gross hematuria and poorer renal prognosis despite of good sensitivity to therapy of proteinuria.

A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody-associated vasculitis.

Glucocorticoids (GCs) are a mainstay of treatment for patients with ANCA-associated vasculitis (AAV) but are associated with significant adverse effects. Effective remission induction in severe AAV using extremely limited GC exposure has not been attempted. We tested an early rapid GC withdrawal induction regimen for patients with severe AAV. Patients with active MPO- or PR3-ANCA vasculitis or ANCA-negative pauci-immune glomerulonephritis were included. Induction treatment consisted of two doses of rituximab, 3 months of low-dose CYC and a short course of oral GC (for between 1 and 2 weeks). Clinical, biochemical and immunological outcomes as well as adverse events were recorded. A total of 49 patients were included, with at least 12 months of follow-up in 46. All patients achieved remission, with decreases observed in creatinine, proteinuria, CRP, ANCA level and BVAS. Three patients requiring dialysis at presentation became dialysis independent. Two patients required the introduction of maintenance GC for treatment of vasculitis. Overall outcomes were comparable to those of two matched cohorts (n = 172) from previous European Vasculitis Society (EUVAS) trials, but with lower total exposure to CYC and GCs (P < 0.001) and reduced rates of severe infections (P = 0.02) compared with the RITUXVAS (rituximab versus cyclophosphamide in AAV) trial. We found no new cases of diabetes in the first year compared with historic rates of 8.2% from the EUVAS trials (P = 0.04). Early GC withdrawal in severe AAV is as effective for remission induction as the standard of care and is associated with reduced GC-related adverse events.

Renal Involvement in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is the most common cause of rapidly progressive glomerulonephritis. ANCAs play an important role in the pathogenesis and diagnosis of AAV. The classic renal lesion in AAV is a pauci-immune necrotizing and crescentic glomerulonephritis. Treatment is divided into 2 phases: (1) induction of remission to eliminate disease activity and (2) maintenance of remission to prevent disease relapse. AAV patients with end-stage renal disease require modification of immunosuppressive strategies and consideration for kidney transplantation. An improved understanding of disease pathogenesis has led to new treatment strategies being tested in clinical trials.

P028 Importance of evaluating allele-level HLA typing of the donor to assess the immunological logistics of importing a renal allograft for highly sensitized recipient and facilitating a successful transplant

Renal transplant candidates with more than 99% CPRA are at greater disadvantage for a match run. Even with a match-run, some of the allelic DSAs not used for Unacceptable Antigens [UA] entry criteria, could make the decision to import an organ from a distant location difficult without knowing the donor’s allele level typing. We describe the case of a patient where the first potential importable organ had to be rejected and the second one could be accepted leading to a successful transplant based on inferred 2 field HLA typing information of the donor. Case: Patient JG, a 24 year old female with a hx of ESRD secondary to pauci-immune glomerulonephritis with a kidney txp in 2001 that failed in 2012 with >99% CPRA got an import kidney offer in Aug 2017 for a donor with an HLA Genotype of A68/-; B35, 39; C1, 7; and DRB1 *0401/04/02/03 at both HLA-DRB1 Loci. The Recipient had strong antibody to DRB1*04:02 [MFI 7000 consistently]and B39MFI = 3117. Since the donor had a potential DRB1*04:02 on both DR4 loci and a B39, the offer was rejected. HLA-DR4 could not be entered as UA despite a high MFI value since listed patient was DRB1*04:01/*04:07. Another offer came through and the donor had a DRB1*04 but the most possible alleles were depicted as DRB1*04: 03/*04:07 and DRB1*04:02 was not an option. So the only HLA DSA the patient had towards this donor was B39 [MFI = 3117]; Accepted the organ and the real cross match was negative, the transplant was done and the Recipient is doing well as of now. Allele-specific antibodies and their impact on real cross matches have been highlighted by failed NKR Chains not knowing allele specific DSAs. Also, when a patient is listed as DRB1*04, we cannot list any UAs as DR4. And as we propagate our ability to assign antibody specificity based on the single antigen bead based assays, we are still at large with allele-specific antibodies that could be crucial. We have an example of a case where the Recipient had antibodies against B*35:01 and DRB1*14:01/02/54; and had a donor with B*35:12 and DRB1*14:07 -And No beads to assess antibodies against B*35:12 or DRB1*14:07. Conclusion: Virtual crossmatch can be an excellent tool as long as we have reliable data on DSAs in terms of the allele-specific antibodies where applicable, and it is extremely important when one make decision to import an organ based on potential allele-specific DSAs.

Primary Vasculitis in Childhood: GPA and MPA in Childhood.

Childhood onset anti-neutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a rare group of primary systemic vasculitides affecting medium and small blood vessels. AAV includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal limited ANCA vasculitis. These disorders are associated with severe clinical manifestations, frequent relapses and a high cumulative morbidity, and often present with multisystem involvement. Renal involvement is common in the pediatric age group, characterized by pauci-immune necrotizing and crescentic glomerulonephritis which frequently progresses to chronic kidney disease in adulthood. ANCAs against proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO) (MPO-ANCA) remain the hallmark of AAV and are integral to the disease pathogenesis. Newer understanding of neutrophil extracellular traps and complement activation have provided better insights into disease pathogenesis. A pediatric vasculitis working group has developed and validated childhood vasculitis classification criteria and disease activity and damage scores. No specific pediatric treatment recommendations exist due to rare nature of the illness in pediatric population. Smaller case series have been published on the efficacy of adult treatment regimens in pediatric patients. The prognosis often remains guarded with frequent relapses and a high cumulative morbidity. The aim of this article is to provide a comprehensive review on pediatric AAV with a focus on recent observations regarding epidemiology, disease pathogenesis, treatment, and prognosis.

Presentación atípica de la poliangeítis microscópica con compomiso renal, pulmonar, dermatológico y del sistema nervioso central

La poliangeítis microscópica (PAM) es una vasculitis autoinmune caracterizada por la inflamación de los vasos sanguíneos de pequeño calibre y la presencia de anticuerpos anticitoplasma de neutrófilos (ANCA). Clínicamente se caracteriza por presentar glomerulonefritis y capilaritis pulmonar aunque la afectación de la piel, los nervios y el tracto gastrointestinal no es infrecuente. Presentamos el caso de un paciente de 17 años con manifestaciones atípicas dadas por glomerulonefritis pauci-inmune, hemorragia pulmonar, vasculitis leucocitoclásica cutánea y hemorragia cerebral. Además revisamos las características histológicas y radiológicas.

A case of microscopic polyangiitis presenting with acute spinal subdural hemorrhage.

This report describes a case of a 62-year-old woman with microscopic polyangiitis (MPA) who developed acute spinal subdural hemorrhage. MPA was confirmed by positive autoantibodies to myeloperoxidase and focal segmental necrotizing and pauci-immune crescentic glomerulonephritis on renal biopsy. She did not recover from paraplegia due to acute spinal subdural hemorrhage, despite decompression operation and aggressive immunosuppression. Although spontaneous spinal hemorrhage in MPA patients is very rare, the prognosis for such patients is poor. Considering the possibility of ongoing vasculitis activity in extra-renal organs, clinicians should be very cautious to attenuate the strength of immunosuppressant drugs, even in patients with chronic or irreversible renal pathology.

Prognostic Factors in Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis with Severe Glomerular Sclerosis: A National Registry-Based Cohort Study.

Background Classification of patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) into histological classes is useful for predicting a patient's risk of progression to end-stage renal disease (ESRD). However, even in the worst prognostic group, the 5-year end-stage renal disease-free survival rate is as high as 50%. Objectives To investigate those prognostic factors indicative of progression to ESRD in patients with ANCA-GN and sclerosing histology. Methods Patients from the Norwegian Kidney Biopsy Registry between 1991 and 2012 who had biopsy verified pauci-immune glomerulonephritis, positive ANCA serology, and sclerosing histology were included. Cases with ESRD during follow-up were identified via linkage with the Norwegian Renal Registry. Potential prognostic factors with relevant cut-offs were compared in patients with and without progression to ESRD during follow-up. Results Of 23 included patients, 10 progressed to ESRD. ESRD patients had a lower initial estimated glomerular filtration rate (eGFR; 21 versus 52 ml/min/1.73 m2) and a lower percentage of normal glomeruli (4% versus 15%). Five-year risks of ESRD with eGFR >15 versus ≤15 ml/min/1.73 m2 were 77% and 15%, with percentage normal glomeruli >10% versus ≤10%, 83% and 39%. Conclusions eGFR and percentage of normal glomeruli are strong risk factors for ESRD in ANCA-GN with sclerosing histology.

Histopathological Classification-A Prognostic Tool for Rapidly Progressive Glomerulonephritis.

Background: Recently proposed histopathological classification may predict patient outcome in pauci-immune glomerulonephritis. This study sought to prove that the prognostic effect could be extended to all types of rapidly progressive glomerulonephritis. Methods: Retrospective analysis of patients diagnosed with rapidly progressive glomerulonephritis between April 1999 and August 2015 was performed. Epidemiological and clinical data were collected from medical records. The descriptions of renal biopsies were reviewed and classified into focal, sclerotic, crescentic and mixed class according to classification proposed by Berden et al. The study end points were end stage renal disease (ESRD) or death. Survival analyses were modelled using Cox regression. Results: 73 renal biopsies with diagnosis of rapidly progressive glomerulonephritis were included in the study. 25 (34.2%), 16 (21.9%), 24 (32.9%) and 8 (11%) patients were assigned to focal, crescentic, mixed and sclerotic class, respectively. Thirty-two (42.5%) patients were anti-neutrophil cytoplasmic antibody (ANCA) negative, of which eight (10.9%) were anti–glomerular basement membrane antibody (anti–GBM) positive and 24 (32.8%) were negative for autoimmune antibodies. Six (8.2%) patients died within one year. Among patients who survived, median change in estimated glomerular filtration rate (eGFR) values were: −10.5 mL/min in focal, 4.2 mL/min in crescentic, −4.3 mL/min in mixed and 4.1 mL/min in sclerotic group, p > 0.05. In the Cox regression model, there was no significant predictor of patient survival whereas the sclerotic group (HR 3.679, 95% CI, 1.164–11.628, p < 0.05) and baseline eGFR of <15 mL/min (HR 4.832, 95% CI, 1.55–15.08, p < 0.01) had an unfavorable effect for renal survival. Conclusions: Predominant glomerular sclerosis and low eGFR at baseline are associated with higher risk of ESRD in cases with crescentic glomerulonephritis. Therefore, despite the origin of injury, histological classification might aid in prediction of patient outcomes in rapidly progressive glomerulonephritis.