Pauci-immune Crescentic Glomerulonephritis Research Articles

Therapeutic Response of Natural Adrenocorotropin in Treatment of Proteinuria due to ANCA Negative Pauci-Immune Crescentic Glomerulonephritis

Therapeutic Response of Natural Adrenocorotropin in Treatment of Proteinuria due to ANCA Negative Pauci-Immune Crescentic Glomerulonephritis

Hydralazine-associated vasculitis: Overlapping features of drug-induced lupus and vasculitis.

Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447.6 or ICD10 code: I77.6, I80, L95, M30, or M31) and positive ANCA lab results over the past 15 years were identified. Age, gender, comorbid conditions, medications taken over the prior 6 months, laboratory data, including electrolytes, urine studies and serologies, chest x-rays, CT scans, and pathologic biopsy records were abstracted from the electronic medical record. 323 cases of AAV were identified, of which 12 were exposed to hydralazine, all at the time of diagnosis. The average duration of hydralazine therapy was 22 months and mean cumulative dose was 146g. Patients were typically older (70.3 years old) with slight female preponderance (7 females). Eleven patients presented with dyspnea, fatigue, and unintentional weight loss. Five had polyarthralgias and 8 had lower extremity petechiae. All 12 patients were both ANA and ANCA positive. ANA titers ranged from 1:160 and 1:2560. Ten were of diffuse pattern while 2 were nucleolar. ANCA titers ranged from 1:320 to 1:2560. Eleven had a pANCA pattern while one had cANCA. All 12 patients were positive for histone and 11 were positive for myeloperoxidase antibodies. Eleven also had dsDNA antibodies, and 4 had anti-cardiolipin IgG or IgM antibodies. Nine patients were also hypocomplementemic (mean C3 level: 88.4mg/dL; mean C4 level: 16.5mg/dL). All patients had variable levels of proteinuria (1+ to 3+) and eleven had active urine sediment. Urine protein:creatinine ratios ranged from 0.2 to 1.7. Of the 6 patients who underwent kidney biopsy, all 6 showed pauci-immune crescentic glomerulonephritis. Seven patients had bilateral pulmonary interstitial infiltrates and four had pleural effusions on CT scan. Four had pericardial effusions as demonstrated by echocardiography. Hydralazine-associated vasculitis is a drug-associated autoimmune syndrome that presents with interstitial lung disease, hypocomplementemia, and pauci-immune glomerulonephritis. Patients have elements of both DIL and DIV, as manifested by high ANA and ANCA titers as well as the presence of histone and MPO antibodies. Further research is needed to understand the etiopathogenesis of this condition.

Importance of renal biopsy in patients aged 60 years and older: Experience from a tertiary care hospital.

As the life expectancy is increasing, there is a rise in elderly population and consequent increase in the patients with renal disease. There is an inconsistency between clinical and histopathological diagnosis in elderly, and so renal biopsy is important in these patients to decide appropriate clinical management and prognosis. This study outlines the importance of renal biopsy in elderly and describes the clinical and pathologic spectrum of renal diseases in patient ≥60 years. All patients (age ≥60 years) undergoing renal biopsies from January 2011 to December 2014 were included in this retrospective study. The clinical presentation and biochemical findings were recorded, and the patients were grouped based on their clinical presentation. Renal biopsies were also evaluated. The mean age of patients was 67.7 ± 6.4 years with a male:female ratio of 3:1. The most common clinical manifestation was nephrotic syndrome (37.4%) followed by rapidly progressive renal failure (RPRF) (20.6%). Amyloidosis and membranous nephropathy were two most common diagnoses in patients with nephrotic presentation whereas pauci-immune crescentic glomerulonephritis and cast nephropathy were common in patients presenting with RPRF. Clinical diagnosis differed from the histopathological diagnosis in 32% cases of nephrotic syndrome. There was good agreement between clinical diagnosis and histology in cases with RPRF. In 73% cases of elderly with (Type II) diabetes suspected of having nondiabetic renal disease clinically, renal biopsy showed evidence of diabetic nephropathy. Renal biopsy is essential in the diagnosis of renal diseases even in elderly. Amyloidosis and membranous nephropathy are common causes of nephrotic syndrome in elderly. Renal biopsy is very useful in diagnosing cast nephropathy and amyloidosis as they are not suspected clinically. It is also helpful in elderly diabetics without retinopathy to differentiate between diabetic and nondiabetic kidney diseases.

ANCA and IgA glomerulonephritis all in one: prognosis and complications

We present the case of a 75-year-old Hispanic woman with known stage 3 chronic kidney disease, long-standing hypertension and type 2 diabetes mellitus who presented with right-sided abdominal pain and...

Medullary Angiitis and Pauci-Immune Crescentic Glomerulonephritis

Although almost all pathological diagnoses made from a native kidney biopsy come from careful examination of the renal cortex, certain diseases have a characteristic medullary component. Medullary angiitis has histological features of interstitial hemorrhage in the medulla with an associated polymorphonuclear leukocyte infiltrate. These findings are primarily found in the setting of antineutrophil cytoplasmic antibody-associated vasculitis. Medullary angiitis identified in the setting of negative immunofluorescence is most suggestive of pauci-immune crescentic glomerulonephritis, as presented in this case.

Clinical, serological and histological determinants of patient and renal outcome in ANCA-associated vasculitis with renal involvement: an analysis from a referral centre.

To evaluate significance of clinical and histopathological prognostic factors for renal and patient outcome in AAV patient cohort. Retrospective study included consecutive patients diagnosed with pauci-immune crescentic glomerulonephritis from January 2003 to December 2013. Primary outcome was combined endpoint patient death or progression to end-stage renal disease (ESRD). Secondary outcomes were patient survival and progression to ESRD (renal survival) singularly and disease relapse. Kaplan-Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Out of 81 patients, 40.7% patients reached primary endpoint, 22.2% died, 29.6% reached ESRD and 16% relapsed during follow-up. Multivariate Cox proportional hazards regression-adjusted analysis found higher BVAS (HR 1.08, 95% CI 1.01-1.17, p=0.042), higher baseline maximal serum creatinine (HR 1.02, 95% CI 1.01-1.03, p=0.04) and lower haemoglobin (HR 0.97, 95% CI 0.95-0.99, p=0.011) significantly associated with primary endpoint. Higher BVAS (HR 1.25, 95% CI 1.01-1.43, p=0.001) and lower haemoglobin (HR 0.95, 95% CI 0.91-0.99, p=0.008) were significantly associated with patient survival, while for renal survival, lower haemoglobin (HR 0.97, 95% CI 0.94-0.99, p=0.041) and the need for acute haemodialysis (HR 3.15, 95% CI 1.20-8.26, p=0.02) were significant predictors. On multivariate-adjusted analysis, no significant predictors for disease relapse were found. Kaplan-Meier survival analysis found no difference between clinical, serological and pathohistological phenotypes for all of the endpoints. Renal function at presentation, anaemia and BVAS should be included in prediction models for the outcomes for the AAV patients.

A tale of two vasculitides: biopsy-proven giant cell arteritis followed by the independent development of renal-limited microscopic polyangiitis

We describe an 80-year-old woman who presented with headaches, bilateral jaw claudication and visual symptoms. She was diagnosed with giant cell arteritis, which was confirmed by temporal artery biopsy. She...

Renal-limited vasculitis with elevated levels of multiple antibodies.

Renal-limited vasculitis (RLV) is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that presents with crescentic glomerulonephritis with no other organ involvement. Although several studies reported patients with crescentic glomerulonephritis who were dual positive for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA or ANCA and anti-glomerular basement membrane (GBM) antibody, patients positive for all three antibodies, i.e., triple-positive patients, were rarely reported. We herein report the case of a male with pauci-immune type crescentic glomerulonephritis positive for MPO-ANCA, PR3-ANCA, and anti-GBM antibody. Renal biopsy led to the definitive diagnosis of RLV with pauci-immune-type crescentic glomerulonephritis. Fluorescence immunostaining showed no linear deposition of IgG on GBM, indicating no involvement of anti-GBM associated diseases. Intensive therapy, including prednisolone, plasma exchange, and intravenous cyclophosphamide, was effective. We report the case of triple-positive patient with crescentic glomerulonephritis, who was successfully treated with glucocorticoid, plasma exchange, and cyclophosphamide, suggesting that treatment for RLV in the patient with serological triple antibodies positivity in the absence of linear IgG deposition could benefit from the combination therapy regimen for plasma exchange and primary induction of remission against microscopic polyangiitis.

Clinicopathological Characteristics and Outcomes of Diffuse Crescentic Glomerulonephritis - A Single Center Experience from Southern India.

Diffuse Crescentic glomerulonephritis (CrGN) is characterized by rapidly progressive renal failure and has grave prognosis. There is significant regional and temporal variation in aetiology, prevalence and prognosis of diffuse crescentic glomerulonephritis (CrGN) with limited data available in adult Indian population. This study aims to identify the aetiology, clinico-pathological features and outcomes of diffuse CrGN in south Indian population. In this retrospective study, clinical records of all adults (>18 years) over a 5-year period (2010-2014) with a histopathological diagnosis of diffuse CrGN (>50% crescents) were reviewed. Clinical, serological, biochemical and histopathological data were collected. Follow-up data at six months including renal outcome and mortality were studied. Data was analysed using SPSS version 15. There were 29 cases of diffuse CrGN accounting for an incidence of 2.9% among 1016 non-transplant kidney biopsies. The most common cause was pauci-immune crescentic GN. The median creatinine at admission was 7.2 mg/dl {(interquartile range (IR) 3.3 - 10.4)} and 75.9% of patients required haemodialysis at admission. Complete/partial recovery was seen in 34.5%. At the end of six months 31% were dialysis dependent and the mortality was 27.6%. On univariate analysis, the significant predictors of renal loss and mortality were oliguria (p=0.02), requirement of haemodialysis and serum creatinine (p=0.001) at admission (>5.5mg/dl) (p=0.003). Histopathological features did not influence the outcome in our study. In our cohort, the most common cause for diffuse CrGN is pauci-immune CrGN. Diffuse CrGN carries a poor prognosis. Patients with pauci-immune and AntiGBM disease have worst prognosis compared to immune complex CrGN. The presence of oliguria, high serum creatinine and requirement of haemodialysis at admission are associated with poor outcomes.

Complement activation in pauci-immune necrotizing and crescentic glomerulonephritis: results of a proteomic analysis.

Complement activation plays an important role in the pathophysiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although it remains unclear which pathway is activated. Whether pauci-immune necrotizing crescentic glomerulonephritis (pauci-immune GN) with negative ANCA serology is part of the spectrum of AAV or a different disease entity is essentially unknown. We used proteomic analysis to delineate the complement profile in a series of 13 kidney biopsies of patients with pauci-immune GN, with either proteinase 3 (PR3) (five patients) or myeloperoxidase (MPO) antibodies (four patients) or with consistently negative ANCA serology (four patients). Immunofluorescence staining of glomeruli was essentially negative in the PR3-ANCA and MPO-ANCA groups, while a mild staining for C3 was seen in the ANCA-negative cases. No electron-dense deposits were found in the PR3-ANCA and MPO-ANCA groups, but mesangial and few subepithelial deposits were clearly present in the ANCA-negative specimens. Mass spectrometry revealed low spectra numbers for C3 and immunoglobulins in both PR3-positive and MPO-positive patients with minimal or no C4 and C9. In contrast, larger spectra numbers for C3, moderate spectra numbers for C9, complement factor H-related protein-1 and low spectra numbers for C4, C5 and immunoglobulins were found in the ANCA-negative cases. While complement activation is noted in AAV, the complement activation appears to be more prominent in the ANCA-negative glomerulonephritis. The larger amount of C3 and moderate amount of C9 in the ANCA-negative glomerulonephritis implies activation of the alternate and terminal pathway of complement, suggesting that this entity may be caused or promoted by a genetic or acquired defect in the alternative pathway.

Pauci-immune crescentic glomerulonephritis associated with use of trimethoprim–sulfamethoxazole

Drug-induced pauci-immune crescentic glomerulonephritis has been described with several agents, including propylthiouracil, minocycline, D-penicillamine, and hydralazine. We present the case of a 60-year-old man who presented with rapidly progressive glomerulonephritis in the setting of recent use of trimethoprim-sulfamethoxazole complicated by the development of the Stevens-Johnson syndrome, and was found to have biopsy-proven pauci-immune crescentic glomerulonephritis and undetectable anti-neutrophilic cytoplasmic antibodies. We review the existing literature on the potential association between sulfonamides and hypersensitivity polyangiitis.

ATYPICAL PRESENTATION IN A CASE OF GRANULOMATOSIS WITH POLYANGIITIS

Granulomatosis with polyangiitis (GPA) is part of the anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis, mostly being ANCA-c (anti proteinase 3) positive. Primarily it involves the upper respiratory tract and kidneys having an increased mortality in the absence of early diagnosis and correct treatment. The most common renal involvement is pauci-immune crescentic glomerulonephritis. We present the case of a patient with GPA with a particular onset of interstitial nephritis, possible by vasa recta vasculitis, in the absence of glomerulonephritis.

The predictive value of kidney biopsy in renal vasculitis: a multicenter cohort study

The histopathologic classification of antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated to have prognostic value in small cohorts of patients with pauci-immune extracapillary glomerulonephritis. We aimed to validate this histologic subgrouping system in a large cohort of patients with renal vasculitis from 3 Spanish centers. The additional value of several histologic parameters for predicting renal outcome was investigated. A total of 151 biopsies of patients with renal vasculitis were reviewed and classified as follows: 41% crescentic, 24% mixed, 21% focal, and 14% sclerotic. The cumulative proportions of renal survival at 5 years were 83.2%, 81.2%, 60.5%, and 50.7% for the focal, mixed, crescentic, and sclerotic categories, respectively (P < .05). In the crescentic category, patients with less than 75% of glomeruli showing crescents had better survival at 1 and 5 years compared with those having greater than or equal to 75% of crescents (77.9% and 70.6% versus 51.3% and 45.6%; P = .02). When adjusted by renal function and other histologic parameters, the percentage of extracapillary proliferation and glomerulosclerosis remained as significant predictors for renal survival (hazard ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .001, and hazard ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .002, respectively). In conclusion, patients with pauci-immune crescentic glomerulonephritis experienced different outcomes depending on the percentage of crescents observed, so that extensive extracapillary proliferation was associated with the poorest renal survival. These findings validate the prognostic utility of the histologic classification scheme in antineutrophil cytoplasmic antibody positive and negative patients and suggest a subdivision of crescentic category (<75% and ≥75% of crescents) based on the different survival rates observed among these subgroups.

Pattern of biopsy-proven kidney disease in the elderly in a tertiary care hospital in India: a clinicopathological study.

An aging population is an important demographic issue in India. The knowledge base about kidney diseases among the elderly Indians is inadequate. We aim to delineate the clinical profile and spectrum of biopsy-proven kidney disease in elderly patients. Records of all elderly patients (≥60 years) who had undergone kidney biopsy in the nephrology department from January 2010 to December 2014 were reviewed. Their clinical details and laboratory investigations at the time of biopsy were noted. Details of kidney biopsy were recorded from their biopsy reports. In total, 1728 patients underwent kidney biopsy during this period and 124 were elderly (7.2%). Their mean age was 64.9 ± 4.9 years, and they were predominantly males (63.7%). Mean serum creatinine was 3.0 ± 2.8 mg/dl, proteinuria was 4.0 ± 2.7 g/day, and 39.5% had microscopic hematuria. The most common indications for biopsy were nephrotic syndrome (NS)--39.5% and acute kidney injury/rapidly progressive glomerulonephritis (AKI/RPGN)--24.2%. Another 8.1% patients had NS with AKI. MN (39.0%) was the chief cause of NS, and pauci-immune crescentic glomerulonephritis (GN) (28.2%) was the leading cause of AKI/RPGN. MN, pauci-immune crescentic GN and acute on chronic tubulointerstitial nephritis (A/CTIN) and acute tubular injury (ATI) were more common in the elderly, while MCD, FSGS, IgA nephropathy and lupus nephritis were more frequent in the younger patients. 68.5% of the elderly patients biopsied were diagnosed with a renal disease which was potentially amenable to specific treatment. The spectrum of biopsy-proven kidney disease in the elderly Indians seen in our tertiary care hospital varies from the younger population. Kidney biopsy provides useful information with therapeutic and prognostic implications in these patients. The percentage of elderly patients among the total biopsied population is low in India, and these patients present late with renal dysfunction. Prospective studies are needed to assess the outcome of the commonly seen kidney diseases in elderly patients.

Granulomatosis with Polyangiitis Presenting as Pauci-Immune Crescentic Glomerulonephritis in Pregnancy.

Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis rarely affects females of reproductive age. A 28-year-old African American woman presented at 8 weeks of gestation with intractable vomiting attributed to hyperemesis gravidarum. She was found to have acute kidney injury that was unresponsive to vigorous fluid resuscitation and urine sediment examination was suggestive of an underlying glomerulonephritis. Serum c-ANCA and PR3 were elevated and there was no peripheral eosinophilia. During her course she also developed one episode of small volume hemoptysis with right upper lobe infiltrates on CT Chest. There were no cutaneous manifestations of vasculitis or upper respiratory symptoms. Renal biopsy revealed a pauci-immune crescentic glomerulonephritis (PICGN). The diagnosis was consistent with granulomatosis with polyangiitis (GPA). Management initially comprised teratogen sparing agents; steroids, intravenous immunoglobulin; and plasma exchange. The response was suboptimal and she became dependent on daily renal replacement therapy. Ultimately the pregnancy was terminated allowing for traditional treatment approaches with dramatic effect. This is the first case of GPA presenting as PICGN in pregnancy and highlights the challenges of its management.

Behçet's Disease and Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis

Behçet's disease (BD) is a multisystem disorder of unknown etiology. Renal involvement in Behçet's disease is not frequent. Pauciimmune necrotizing and crescentic glomerulonephritis is associated with antineutrophil cytoplasmic antibodies (ANCA) which are believed to activate neutrophils and cause vasculitis, especially if there is a concurrent synergistic inflammatory process. In this case report, we describe a patient diagnosed with BD who also developed pauciimmune necrotizing and crescentic glomerulonephritis. We also compared this case with similar previous cases reported in the literature. The aim of this study is to add information regarding ANCA, pauciimmune glomerulonephritis and Behçet's disease.

PROBLEMS IN THE DIAGNOSIS AND TREATMENT OF ANCA-ASSOCIATED SYSTEMIC VASCULITIS: IN THE FOCUS OF ANCA-NEGATIVE PAUCI-IMMUNE GLOMERULONEPHRITIS

One of the most common causes of rapidly progressive glomerulonephritis (GN) is the so-called pauci-immune crescentic GN that is characterized by no luminescence in kidney tissue samples during immunofluorescence microscopy and by the hyperproduction of antineutrophil cytoplasmic antibodies (ANCA). At the same time, serum ANCAs are absent in a number of cases of pauci-immune GN. Based on their own experience, the authors present the clinical and morphological characteristics of patients with ANCA-negative pauci-immune GN and analyze the data available in the literature. Subjects and methods. This retrospective study included 8 patients with ANCA-negative pauci-immune GN, who were followed up at two Russian centers (the Center of Nephrology and the Center of Rheumatology) in 2011 to 2015. Results and discussion. According to our data, ANCAs are not detectable in 6% of the patients with ANCA-associated systemic vasculitis (SV) with renal involvement and/or pauci-immune GN. The mean age at onset of the disease in the ANCA-negative patients was 50±18 years (range 19 to 74 years); the male/female ratio was 1:1. Four (50%) cases were diagnosed with microscopic polyangiitis; 2 cases had granulomatosis with polyangiitis; isolated renal injury was present in other 2 patients. The Birmingham SV activity index averaged 19.6±7.9. Hematuria was observed in all cases and it was massive in 4. The mean daily urinary protein level was 3.4±2.7 g; three (38%) patients were observed to have nephrotic syndrome. The blood creatinine level averaged 704±405 μmol/l; GN was characterized by a rapidly progressive course in 6 (75%) patients; hemodialysis was needed in 5. A morphological study of the kidney determined crescents (in on an average of 52 glomeruli) in the majority of cases and glomerulosclerosis in one patient. All the patients were observed to have varying degrees of interstitial fibrosis. Three (38%) treated patients achieved remission. The mortality rates were 38%. Interestingly, the data from our group as well those obtained by the study of European cohorts were slightly different from those of the studies conducted in Asia, according to which a renal biopsy more frequently revealed glomerular crescents; the levels of protein in the urine were higher and renal survival was worse. Thus, serum ANCAs are absent in 3–39% of cases of pauci-immune crescentic GN, but the clinical and morphological picture corresponds to ANCA-associated SV. A kidney biopsy helps establish the correct diagnosis, timely use induction treatment, and improve prognosis.

Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease.

Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe.

Eosinophilic Granulomatous Polyangitis with Renal Granulomatous Angitis and Interstitial Eosinophilic Infiltration without Lung Granuloma

Eosinophilic granulomatous with polyangiitis (EGPA) is systemic vasculitis characterized by concomitant symptoms of asthma, allergic rhinitis, and marked increase in peripheral eosinophilia. It was previously known as Churg-Strauss syndrome. EGPA incidence in Japan is very low, with only approximately 1,800 cases reported. Renal involvement occurs in approximately 20-25% of EGPA patients, and the most typical expression is pauciimmune crescentic glomerulonephritis. We herein report a case of 69-year-old Japanese woman with fever and high titer of myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) and eosinophilia. Her renal biopsy showed massive interstitial nephritis with granulomatous vasculitis like lesion without apparent active crescent formation in glomeruli. Immediately after steroid treatment (prednisolone [PSL] 30 mg/day), she had symptomatic relief and was discharged with a reduction in MPO-ANCA.

Necrotizing and crescentic glomerulonephritis with membranous nephropathy in a patient exposed to levamisole-adulterated cocaine.

Levamisole is an antihelminthic agent widely used as an adulterant of illicit cocaine recently implicated as a cause of antineutrophil cytoplasmic antibody (ANCA)–associated microscopic polyangiitis in cocaine abusers. An isolated case of membranous nephropathy (MN) associated with levamisole exposure has also been reported. We report the first case, to our knowledge, of a patient with both microscopic polyangiitis manifest as a pauci-immune necrotizing and crescentic glomerulonephritis and concurrent MN in the setting of chronic cocaine abuse and presumed levamisole exposure, raising the hypothesis that levamisole was the causative agent in the development of this rare dual glomerulopathy.